WO2024216391A1

WO2024216391A1 - Method of diagnosis and treatment of pancreatic cancer

Info

Publication number: WO2024216391A1
Application number: PCT/CA2024/050507
Authority: WO
Inventors: Mohammad Ashraful Anwar; Zhengnan Wang; Ana MADDOX; Robert Fraser
Original assignee: Molecular You Corp
Current assignee: Molecular You Corp
Priority date: 2023-04-19
Filing date: 2024-04-18
Publication date: 2024-10-24
Anticipated expiration: 2025-10-19
Also published as: AU2024257583A1

Abstract

According to the present disclosure, a new proteomic profile for pancreatic cancer is used to treat and/or ameliorate pancreatic cancer. In some embodiments, the treatment comprises removing cancerous tissue after a biopsy is obtained from the patient. Optionally the treatment comprises administering an anti-cancer therapeutic agent for reducing pancreatic cancer progression. In additional or alternative embodiments, the new proteomic profile is used to monitor disease progression or remission.

Description

METHOD OF DIAGNOSIS AND TREATMENT OF PANCREATIC CANCER

TECHNICAL FIELD

[0001] The present disclosure relates generally to the field of diagnosing and treating pancreatic cancer.

BACKGROUND

[0002] Pancreatic cancer has poor prognosis. This is often because early detection is difficult. Patients usually have no symptoms until the cancer is untreatable and/or has spread throughout the body. Moreover, tumours are difficult to visualize since they are located deep within the body.

[0003] With an aim to diagnose the disease early, genetic testing is conducted for those patients with a family history of the disease. Such tests examine gene changes that cause inherited conditions. However, these tests have limitations in their ability to predict pancreatic cancer risk. For individuals identified as having a risk of developing pancreatic cancer through genetic testing, an endoscopic ultrasound or magnetic resonance imaging (MRI) is still used to assess the likelihood of pancreatic cancer. While doctors have been able to find early, treatable pancreatic cancers in members of the public pre-disposed to developing pancreatic cancer by genetic analyses, such tests are not used to screen the general public. (See American Cancer Society: www.cancer.or /cancer/pancreatic-cancer/detection-dia nosis-sta in /detection.html).

[0004] In addition, few drugs are available to treat pancreatic cancer. In the past few years, numerous targeted agents have been tested, such as ECFR inhibitors (erlotinib), VEGF and VEGFR inhibitors, phosphoinositide-3-kinase-mTOR pathway inhibitors, Janus kinase inhibitors, and Ras pathway inhibitors. Unfortunately, most of these agents were ineffective at treating the disease (Zhu et al., 2018, “Pancreatic cancer: challenges and opportunities”, BMC Medicine 16(214)).

[0005] Accordingly, pancreatic cancer is not only difficult to detect early, but remains one of the most untreatable forms of cancer in humans.

[0006] Thus, there is a need for an improved method for the diagnosis of pancreatic cancer, and/or to determine a subject’s predisposition for developing pancreatic cancer, and treatment thereof. There also exists a need for the screening and treatment of individuals with early stage (e.g., stage 1 or 2) pancreatic cancer.

SUMMARY

[0007] The present disclosure provides a method for diagnosing and treating or causing the treating of pancreatic cancer.

[0008] According to the present disclosure, a new proteomic profile for pancreatic cancer is used to diagnose and treat and/or ameliorate pancreatic cancer. In some embodiments, the treatment comprises surgery to remove the tumour or optionally administering an anti-cancer therapeutic agent, e.g., for reducing pancreatic cancer progression. In additional or alternative embodiments, the new proteomic profile is used to monitor disease progression and/or remission.

[0009] The proteomic profile for pancreatic cancer comprises at least one, at least two, at least three, at least four, at least five, at least six or at least seven pancreatic cancer-related proteins selected from apolipoprotein Al, apolipoprotein A-II, plasma protease Cl inhibitor, L-selectin, tetranectin, phospholipid transfer protein, apolipoprotein M, gelsolin, adipocyte plasma membrane-associated protein, Cis complement factor, C4b complement factor or C6 complement factor and fibronectin. In one embodiment, a subject is diagnosed as having pancreatic cancer by determining whether one, two, three, four, five, six, seven or more of the proteins are elevated, such as elevated by at least 1.2 times, 1.4 times, 1.6 times, 1.8 times, 2.0 times or more relative to a level that is considered normal (e.g., a baseline) in a subject(s) without pancreatic cancer.

[0010] It has been surprisingly found that the proteomic profile comprising a plurality of the foregoing proteins or peptide fragments thereof is elevated in a subject suffering from early-stage pancreatic cancer (stage 1) as compared to a pancreatic cancer- negative individual. In some embodiments, the levels of the pancreatic cancer-related proteins are elevated in the circulation of the subject having pancreatic cancer as compared to an individual without pancreatic cancer. In further embodiments, the levels of pancreatic cancer-related proteins in circulation of the subject are monitored as described herein and if changes over time are detected, the subject is identified for further assessment. In certain embodiments, the levels of the pancreatic cancer-related proteins are altered in the blood (e.g., serum, plasma), body fluids (e.g., cerebrospinal fluid, pleural fluid, amniotic fluid, semen, or saliva), urine, and/or feces of the subject having pancreatic cancer. Without wishing to be bound by theory, it is believed that the novel combination of pancreatic cancer-related proteins plays a role in the development of pancreatic cancer. The treatment method may further comprise a step or steps of obtaining a biopsy to positively confirm the presence of pancreatic cancer followed by surgery and/or administration of a pancreatic cancer drug. Typically, the treatment comprises a combination of a biopsy and surgery after a positive diagnosis.

[0011] According to one aspect of the disclosure, there is provided a method for treating pancreatic cancer in a subject, the method comprising: (i) receiving a proteomic profile from a subject, the proteomic profile previously obtained by: (a) providing a biological sample obtained from the subject; (b) measuring concentration levels of one or a combination of, at least two, at least three, at least four or at least five pancreatic cancer-related proteins, or peptide fragment thereof, selected from apolipoprotein Al, apolipoprotein A-II, plasma protease Cl inhibitor, L-selectin, tetranectin, phospholipid transfer protein, apolipoprotein M, gelsolin, adipocyte plasma membrane-associated protein, Cis complement factor, C4b complement factor, C6 complement factor and fibronectin from the obtained sample; (c) comparing the concentration levels of the pancreatic cancer-related proteins, or peptide fragments thereof, from the obtained sample to the concentration levels of reference pancreatic cancer-related proteins or peptide fragments thereof from a pancreatic cancernegative reference value and/or from a sample obtained at an earlier time point from the subject; (ii) identifying the subject as being at risk of having pancreatic cancer if the concentration levels of the pancreatic cancer-related proteins, or peptide fragments thereof, from the obtained sample are different relative to the concentration levels of the reference pancreatic cancer-related proteins or peptide fragments thereof, from the pancreatic cancer-negative reference value and/or from a sample obtained at an earlier time point from the subject; (iii) optionally obtaining a biopsy from the subject so identified as being at risk of having pancreatic cancer in step (ii); (iv) analyzing the biopsy to determine if cancerous cells are present; (v) identifying the subject as having pancreatic cancer if the subject is identified as being at risk of having pancreatic cancer based on the proteomic profile in step (ii) and if the cancerous cells are present in the biopsy; and (vi) optionally removing the cancerous tissue from the subject’s pancreas and/or bile duct(s) if the subject is identified as having pancreatic cancer. [0012] According to a further aspect of the disclosure, there is provided a method for diagnosing and treating pancreatic cancer in a subject, the method comprising: (a) providing a biological sample obtained from the subject; (b) measuring concentration levels of one or a combination of, at least two, at least three, at least four or at least five pancreatic cancer-related proteins, or peptide fragment thereof, selected from apolipoprotein Al, apolipoprotein A-II, plasma protease Cl inhibitor, L-selectin, tetranectin, phospholipid transfer protein, apolipoprotein M, gelsolin, adipocyte plasma membrane-associated protein, Cis complement factor, C4b complement factor, C6 complement factor and fibronectin from the obtained sample; (c) comparing the concentration levels of the pancreatic cancer-related proteins, or peptide fragments thereof, from the obtained sample to the concentration levels of reference pancreatic cancer-related proteins or peptide fragments thereof from a pancreatic cancer-negative reference value and/or from a sample obtained at an earlier time point from the subject; (d) identifying the subject as having pancreatic cancer or at risk of having pancreatic cancer if the concentration levels of the pancreatic cancer- related proteins, or peptide fragments thereof, from the obtained sample are different relative to the concentration levels of the reference pancreatic cancer-related proteins or peptide fragments thereof, from the pancreatic cancer-negative reference value and/or from a sample obtained at an earlier time point from the subject; and (e) optionally treating or causing the treating of the subject so identified as having pancreatic cancer with a pancreatic cancer treatment regime, optionally comprising surgery and/or administration of a chemotherapeutic agent or radiation treatment.

[0013] According to a further aspect of the disclosure, there is provided a method for diagnosing and treating pancreatic cancer in a subject, the method comprising: (a) providing a biological sample obtained from the subject; (b) measuring or having measured in a spectroscopy unit the concentration levels of a combination of pancreatic cancer-related proteins, or peptide fragments thereof, selected from selected from apolipoprotein Al; apolipoprotein A-II, plasma protease Cl inhibitor, L-selectin, tetranectin, phospholipid transfer protein, apolipoprotein M, gelsolin, adipocyte plasma membrane-associated protein, Cis complement factor, C4b complement factor, C6 complement factor and fibronectin from the obtained sample; (c) comparing or having compared concentration levels of the pancreatic cancer-related proteins, or peptide fragments thereof, as determined in the spectroscopy unit to the concentration levels of reference pancreatic cancer- related proteins, or peptide fragments thereof, from a pancreatic cancer-negative reference value and/or from a sample obtained at an earlier time point from the subject; (d) identifying the subject as having pancreatic cancer or at risk of having pancreatic cancer if the concentration levels of the pancreatic cancer-related proteins, or peptide fragments thereof, from the obtained sample are different relative to the concentration levels of the reference pancreatic cancer-related proteins, or peptide fragments thereof, from the pancreatic cancer-negative sample and/or from a sample obtained at an earlier time point from the subject; and (e) optionally treating or causing the treating of the subject so identified as having pancreatic cancer with a pancreatic cancer treatment regime, optionally comprising surgery and/or administration of a chemotherapeutic agent or radiation treatment.

[0014] In one embodiment, the pancreatic cancer treatment comprises lowering the blood levels of one or more of the pancreatic cancer-related proteins or peptide fragments thereof in the subj ect diagnosed as having the pancreatic cancer.

[0015] According to any one of the foregoing aspects or embodiments, the adjustment of the blood levels of one or more of the pancreatic cancer-related proteins or peptide fragments thereof in the subject occurs until the pancreatic cancer-related proteins or peptide fragments thereof are lowered to a predetermined level in the subject.

[0016] According to any one of the foregoing aspects or embodiments, the identifying step occurs upon determination that the concentration levels of at least one, at least two, at least three, at least four or at least five of the pancreatic cancer-related proteins or peptide fragments thereof from the obtained sample are elevated by about 10% or more, 20% or more, about 30% or more, about 40% or more, about 50% or more, about 60% or more, or about 70% or more relative to the concentration levels of the reference pancreatic cancer-related proteins or peptide fragments thereof from the pancreatic cancer-negative reference value and/or relative to concentrations levels in a sample obtained previously from the subject.

[0017] According to any one of the foregoing aspects or embodiments, measuring the concentration levels of the pancreatic cancer-related proteins or peptide fragments comprises measuring at least one, at least two, least three, or each one of L-selectin, tetranectin, phospholipid transfer protein and fibronectin. [0018] According to any one of the foregoing aspects or embodiments, the concentration level of at least tetranectin is measured.

[0019] According to any one of the foregoing aspects or embodiments, the obtained sample is blood or urine.

[0020] According to any one of the foregoing aspects or embodiments, the obtained sample is serum or plasma.

[0021] According to any one of the foregoing aspects or embodiments, the obtained sample is urine.

[0022] According to any one of the foregoing aspects or embodiments, the pancreatic cancer- related proteins or peptide fragments thereof are measured by a spectroscopic technique, wherein the spectroscopic technique is selected from the group consisting of liquid chromatography, gas chromatography, liquid chromatography mass spectrometry, gas chromatography mass spectrometry, high performance liquid chromatography mass spectrometry, capillary electrophoresis mass spectrometry, nuclear magnetic resonance spectrometry (NMR), raman spectroscopy and infrared spectroscopy.

[0023] According to any one of the foregoing aspects or embodiments, the spectroscopic technique comprises mass spectrometry.

[0024] According to any one of the foregoing aspects or embodiments, the comparison of the concentration levels of the pancreatic cancer-related proteins or peptide fragments thereof or peptide fragments thereof from the obtained sample to the concentration levels of the reference values comprises using multivariate statistical analysis.

[0025] According to any one of the foregoing aspects or embodiments, the multivariate statistical analysis is selected from principal component analysis (PCA), or partial least squares projects to latent structures discriminant analysis (PLS-DA).

[0026] According to another aspect of the disclosure, there is provided a method of monitoring protein or peptide fragments in a subject and treating pancreatic cancer in a subject, the method comprising: (a) providing a first biological sample obtained from the subject at a first time point; (b) assessing a first pancreatic cancer-related proteomic profile by measuring concentration levels of at least one, at least two, at least three, at least four or at least five pancreatic cancer-related proteins, or peptide fragments thereof, selected from pancreatic cancer-related proteins or peptide fragments thereof selected from apolipoprotein Al; apolipoprotein A-II, plasma protease Cl inhibitor, L-selectin, tetranectin, phospholipid transfer protein, apolipoprotein M, gelsolin, adipocyte plasma membrane-associated protein, Cis complement factor, C4b complement factor, C6 complement factor and fibronectin from the first biological sample; (c) comparing the first pancreatic cancer-related proteomic profile with a reference pancreatic cancer-related proteomic profile from a pancreatic cancer-negative sample; (d) determining that there is a first difference between the first pancreatic cancer-related proteomic profile and the reference pancreatic cancer- related proteomic profile from the pancreatic cancer-negative sample, the first difference being indicative of pancreatic cancer; (e) providing a second biological sample obtained from the subject at a second time point that is after the first time point; (f) assessing a second pancreatic cancer- related proteomic profile by measuring concentration levels of the pancreatic cancer-related proteins or peptide fragments thereof from the second biological sample; (g) comparing the second pancreatic cancer-related proteomic profile with the reference pancreatic cancer-related proteomic profile from the pancreatic cancer-negative sample; (h) determining that there is a second difference between the first pancreatic cancer-related proteomic profile and the reference pancreatic cancer-related proteomic profile from the pancreatic cancer-negative sample, the second difference being indicative of pancreatic cancer; (i) determining pancreatic cancer progression or a risk of having pancreatic cancer based at least in part on the first and second differences; and (j) optionally treating or causing the treating of the subject if identified as having pancreatic cancer with a pancreatic cancer treatment regime, optionally comprising surgery and/or administration of an anti-cancer therapeutic agent or radiation treatment.

[0027] According to the foregoing aspect, in some embodiments, the period of time between the first time and the second time points is at least 1 month, at least 2 months, at least 3 months or at least 6 months.

[0028] According to the foregoing aspect or embodiments thereof, measuring the concentration levels of the pancreatic cancer-related proteins or peptide fragments thereof from the first and/or second biological samples comprises measuring at least one, at least two, least three, or each one of L-selectin, tetranectin, phospholipid transfer protein and fibronectin.

[0029] According to the foregoing aspect or embodiments thereof, the concentration level of at least tetranectin is measured.

[0030] According to the foregoing aspect or embodiments thereof, the first sample, the second sample, or both are blood or urine or wherein both samples are the same specimen type and are selected from serum, plasma or urine.

[0031] According to a further aspect of the disclosure, there is provided a kit for diagnosis of pancreatic cancer comprising: (a) a detector configured to detect concentration levels of at least one, at least two, at least three, at least four or at least five pancreatic cancer-related proteins, or peptide fragments thereof, selected from apolipoprotein Al; apolipoprotein A-II, plasma protease Cl inhibitor, L-selectin, tetranectin, phospholipid transfer protein, apolipoprotein M, gelsolin, adipocyte plasma membrane-associated protein, Cis complement factor, C4b complement factor, C6 complement factor and fibronectin obtained from a biological sample; (b) a composition comprising apolipoprotein Al; apolipoprotein A-II, plasma protease Cl inhibitor, L-selectin, tetranectin, phospholipid transfer protein, apolipoprotein M, gelsolin, adipocyte plasma membrane-associated protein, Cis complement factor, C4b complement factor, C6 complement factor and fibronectin in control levels corresponding to a control group of pancreatic cancernegative subjects; (c) a multivariate analysis system configured to analyze a difference in the concentration levels of the pancreatic cancer-related proteins or peptide fragments thereof and the control levels, and (d) optionally, providing instructions for a pancreatic cancer diagnosis method, wherein the method comprises measuring, using the detector, the levels of the pancreatic cancer- related proteins or peptide fragments thereof from the obtained biological sample, and comparing the levels of the obtained pancreatic cancer-related proteins or peptide fragments thereof to the control levels of the pancreatic cancer-related proteins or peptide fragments thereof obtained from pancreatic cancer-negative subjects and/or from a sample obtained at an earlier time point from the subject.

[0032] According to one embodiment of the foregoing aspect of the disclosure, the detector comprises a multi -proteomic detector configured to measure the levels of the pancreatic cancer- related proteins, or peptide fragments thereof, comprising the apolipoprotein Al, apolipoprotein A-II, plasma protease Cl inhibitor, L-selectin, tetranectin, phospholipid transfer protein, apolipoprotein M, gelsolin, adipocyte plasma membrane-associated protein, Cis complement factor, C4b complement factor, C6 complement factor and fibronectin.

[0033] In some embodiments of the foregoing aspect or embodiments thereof, the detector is configured to measure the concentration levels of the pancreatic cancer-related proteins or peptide fragments comprising at least one, at least two, least three, or each one of L-selectin, tetranectin, phospholipid transfer protein and fibronectin.

[0034] In some embodiments of the foregoing aspect or embodiments thereof, the detector is configured to measure at least tetranectin.

[0035] According to a further aspect of the disclosure, there is provided a computer-implemented method for processing a biological sample of a subject, diagnosing pancreatic cancer and treating the pancreatic cancer, the computer-implemented method comprising: (a) receiving a biological sample obtained from the subject; (b) processing the sample in a spectroscopy unit directly or wirelessly linked to a processing device, the processing device having memory for storing measurement data from the spectroscopy unit; (c) in the spectroscopy unit, measuring levels of least one, at least two, at least three, at least four or at least five pancreatic cancer-related proteins, or peptide fragments thereof, selected from apolipoprotein Al, apolipoprotein A-II, plasma protease Cl inhibitor, L-selectin, tetranectin, phospholipid transfer protein, apolipoprotein M, gelsolin, adipocyte plasma membrane-associated protein, Cis complement factor, C4b complement factor or C6 complement factor and fibronectin and storing the measurement data in the processor; (d) comparing the stored measurement data to a reference value in the memory representing a pancreatic cancer- negative sample, optionally using multivariate statistical analysis; (e) storing on the processing device a result corresponding to at least one, at least two, at least three, at least four or at least five pancreatic cancer-related proteins or peptide fragments thereof selected from the group consisting of apolipoprotein Al, apolipoprotein A-II, plasma protease Cl inhibitor, L-selectin, tetranectin, phospholipid transfer protein, apolipoprotein M, gelsolin, adipocyte plasma membrane-associated protein, Cis complement factor, C4b complement factor or C6 complement factor and fibronectin from the obtained sample, wherein the result identifies the subject as having pancreatic cancer or a risk of having pancreatic cancer if the measurement data representing the levels of the pancreatic cancer-related proteins or peptide fragments thereof are different relative to a concentration levels of reference pancreatic cancer- related proteins, or peptide fragments thereof, from a pancreatic cancer-negative sample; (f) displaying the result on an electronic display connected directly or wirelessly to the processor for the subject identified as having pancreatic cancer, a risk of having pancreatic cancer or as having a predisposition of developing pancreatic cancer; and (g) optionally treating or causing treatment of the subject identified as having pancreatic cancer with a pancreatic cancer regime, optionally comprising surgery and/or administration of an anti-cancer therapeutic agent or radiation treatment.

[0036] In some embodiments of the foregoing aspect or embodiments thereof, the displayed result is included in a user interface that is a dashboard.

[0037] In some embodiments of the foregoing aspect or embodiments thereof, the displayed result is part of multi-omic information displayed on the user interface.

[0038] In some embodiments of the foregoing aspect or embodiments thereof, the spectroscopy unit comprises a detector or is operatively connected to a detector that is configured to measure the concentration levels of the pancreatic cancer-related proteins or peptide fragments optionally configured to measure at least one, at least two, least three, or each one of L-sel ectin, tetranectin, phospholipid transfer protein and fibronectin.

[0039] In some embodiments of the foregoing aspect or embodiments thereof, the detector is configured to measure at least tetranectin.

[0040] According to a further aspect of the disclosure, there is provided a method for diagnosing and treating pancreatic cancer in a subject, the method comprising: (a) providing a biological sample obtained from the subject; (b) measuring concentration levels of at least one, at least two, at least three, at least four or at least five pancreatic cancer-related proteins or peptide fragments thereof selected from apolipoprotein Al, apolipoprotein A-II, plasma protease Cl inhibitor, L- selectin, tetranectin, phospholipid transfer protein, apolipoprotein M, gelsolin, adipocyte plasma membrane-associated protein, Cis complement factor, C4b complement factor or C6 complement factor and fibronectin; (c) comparing the concentration levels of the pancreatic cancer-related proteins or peptide fragments thereof from the obtained sample to the concentration levels of reference pancreatic cancer-related proteins or peptide fragments thereof from a pancreatic cancernegative sample and/or from a sample obtained at an earlier time point from the subject; (d) identifying the subject as having pancreatic cancer or a risk of having pancreatic cancer if the concentration levels of the pancreatic cancer-related proteins or peptide fragments thereof from the obtained sample are different relative to the concentration levels of the reference pancreatic cancer-related proteins or peptide fragments thereof from the pancreatic cancer-negative sample and/or from a sample obtained at an earlier time point from the subject; and (e) optionally treating or causing the treating of the subject so identified with a pancreatic cancer treatment regime or radiation treatment.

[0041] In some embodiments of the foregoing aspect or embodiments thereof, measuring the concentration levels of the pancreatic cancer-related proteins or peptide fragments thereof from the first and/or second biological samples comprises measuring at least one, at least two, least three, or each one of L-selectin, tetranectin, phospholipid transfer protein and fibronectin.

[0042] In some embodiments of the foregoing aspect or embodiments thereof, the concentration level of at least tetranectin is measured.

[0043] According to a further aspect of the disclosure, there is provided a method for diagnosing and treating pancreatic cancer in a subject, the method comprising: (a) providing a first biological sample obtained from the subject; (b) at a first time point, measuring concentration levels of at least one, at least two, at least three, at least four or at least five pancreatic cancer-related proteins or peptide fragments thereof selected from apolipoprotein Al, apolipoprotein A-II, plasma protease Cl inhibitor, L-selectin, tetranectin, phospholipid transfer protein, apolipoprotein M, gelsolin, adipocyte plasma membrane-associated protein, Cis complement factor, C4b complement factor or C6 complement factor and fibronectin from the obtained sample; (c) comparing the concentration levels of the pancreatic cancer-related proteins or peptide fragments thereof from the obtained sample to the concentration levels of reference pancreatic cancer-related proteins or peptide fragments thereof from a pancreatic cancer- negative sample and/or from a sample obtained at an earlier time point from the subject; (d) at a second time point, measuring concentration levels of at least one, at least two, at least three, at least four or at least five pancreatic cancer-related proteins or peptide fragments thereof selected from apolipoprotein Al; apolipoprotein A-II, plasma protease Cl inhibitor, L-selectin, tetranectin, phospholipid transfer protein, apolipoprotein M, gelsolin, adipocyte plasma membrane-associated protein, Cis complement factor, C4b complement factor or C6 complement factor and fibronectin in a second biological sample obtained from the subject; (e) comparing the concentration levels at the second time point of the pancreatic cancer-related proteins or peptide fragments thereof from the obtained sample to the concentration levels of reference pancreatic cancer-related proteins or peptide fragments thereof from a pancreatic cancer- negative sample and/or from a sample obtained at the first time point or the earlier time point from the subject; (f) identifying the subject as having pancreatic cancer or a risk of having pancreatic cancer if the concentration levels of the pancreatic cancer-related proteins or peptide fragments thereof from the first and second obtained samples are different relative to the concentration levels of the reference pancreatic cancer-related proteins or peptide fragments thereof from the pancreatic cancer-negative sample, and/or relative to a sample obtained at the first time point; and (g) optionally treating or causing the treating of the subject if so identified as having pancreatic cancer with a pancreatic cancer treatment regime.

[0044] In some embodiments of the foregoing aspect or embodiments thereof, the identifying step (f) occurs upon determination that the concentration levels of at least one, at least two, at least three, at least four, or at least five of the pancreatic cancer-related proteins or peptide fragments thereof from the obtained sample are elevated by about 10% or more, about 20% or more, about 30% or more, about 40% or more, about 50% or more, about 60% or more, or about 70% or more relative to the concentration levels of the reference pancreatic cancer-related proteins or peptide fragments thereof from the pancreatic cancer-negative sample.

[0045] In some embodiments of the foregoing aspect or embodiments thereof, the identifying step (f) occurs upon determination that the concentration levels of at least three, at least four, or at least five of the pancreatic cancer-related proteins or peptide fragments thereof from the obtained sample are elevated by about 10% or more, about 20% or more, about 30% or more, about 40% or more, about 50% or more, about 60% or more or about 70% or more relative to the concentration levels of the reference pancreatic cancer-related proteins or peptide fragments thereof from the pancreatic cancer-negative sample. [0046] In some embodiments of the foregoing aspect or embodiments thereof, measuring the concentration levels of the pancreatic cancer-related proteins or peptide fragments thereof from the first and/or second biological samples comprises measuring at least one, at least two, least three, or each one of L-selectin, tetranectin, phospholipid transfer protein and fibronectin.

[0047] In some embodiments of the foregoing aspect or embodiments thereof, the concentration level of at least tetranectin is measured.

[0048] In some embodiments of the foregoing aspect or embodiments thereof, the obtained sample is blood or urine, or is serum, plasma or urine.

[0049] In some embodiments of the foregoing aspect or embodiments thereof, the pancreatic cancer-related proteins or peptide fragments thereof are measured by a spectroscopic technique, wherein the spectroscopic technique is selected from the group consisting of liquid chromatography, gas chromatography, liquid chromatography mass spectrometry, gas chromatography mass spectrometry, high performance liquid chromatography mass spectrometry, capillary electrophoresis mass spectrometry, nuclear magnetic resonance spectrometry (NMR), raman spectroscopy, and infrared spectroscopy.

[0050] In some embodiments of the foregoing aspect or embodiments thereof, the comparison of the concentration levels of the pancreatic cancer-related proteins or peptide fragments thereof from the obtained sample to the concentration levels of the reference pancreatic cancer-related proteins or peptide fragments thereof from the pancreatic cancer-negative sample comprises multivariate statistical analysis.

[0051] In some embodiments of the foregoing aspect or embodiments thereof, measuring the concentration levels of the pancreatic cancer-related proteins or peptide fragments thereof from the second biological sample comprises measuring at least one, at least two, least three, or each one of L-selectin, tetranectin and phospholipid transfer protein and wherein if the measured levels of L-selectin, tetranectin and/or phospholipid transfer protein in the second biological sample, when compared to respective concentration levels measured at the first time point, are elevated by at least 10%, 15%, 20% or 25%, the subject is identified as having pancreatic cancer or as having a risk of having pancreatic cancer. [0052] In some embodiments of the foregoing aspect or embodiments thereof, the concentration level of at least fibronectin is measured and wherein if the measured level of fibronectin in the second biological sample, when compared to a respective concentration level measured at the first time point, is elevated or decreased by at least 10%, 15%, 20% or 25%, the subject is identified as having pancreatic cancer or as having a risk of having pancreatic cancer.

[0053] According to a further aspect, there is provided a proteolyzed sample for use in mass spectrometry to diagnose pancreatic cancer in a subject comprising one or a combination of peptide fragments of apolipoprotein Al, apolipoprotein A-II, plasma protease Cl inhibitor, L-selectin, tetranectin, phospholipid transfer protein, apolipoprotein M, gelsolin, adipocyte plasma membrane-associated protein, Cis complement factor, C4b complement factor, C6 complement factor and fibronectin.

[0054] According to a further aspect, there is provided a proteolyzed sample for use in mass spectrometry to diagnose pancreatic cancer in a subject comprising a peptide fragment of L- selectin, tetranectin, phospholipid transfer protein and/or fibronectin.

[0055] In some embodiments of any one of the foregoing aspects or embodiments thereof, the method further comprises obtaining a biopsy sample from the subject identified as having a risk of having pancreatic cancer after measurement of the pancreatic cancer proteins or fragments thereof and if cancerous cells are identified in the sample, surgically removing cancerous tissue from the pancreas and/or bile duct(s) of the subject.

[0056] In some alternative embodiments of any one of the foregoing aspects or embodiments thereof, levels of the tetranectin increase over time as measured at two or more time points within in a 1 -month to 3 -year time period or are elevated at a single time point over a control, thereby identifying the subject as having pancreatic cancer (e.g., stage 1). Such embodiment may further comprise measuring levels of at least one of L-selectin and phospholipid transfer protein, and wherein the levels of at least one of L-selectin and phospholipid transfer protein increase over time as measured at two or more time points within a 1 -month to 3 -year time period or are elevated at a single time point over a control. In some embodiments, the method or kit further comprises measuring fibronectin. In some embodiments, the method further comprises measuring at least one of apolipoprotein Al, apolipoprotein A-II, plasma protease Cl inhibitor, apolipoprotein M, gelsolin, adipocyte plasma membrane-associated protein, Cis complement factor, C4b complement factor, C6 complement factor or a combination thereof.

[0057] All features of exemplary embodiments which are described in this disclosure and are not mutually exclusive can be combined with one another. Elements of one embodiment can be utilized in the other embodiments without further mention. Other aspects and features of the present disclosure will become apparent to those ordinarily skilled in the art upon review of the following description of specific embodiments in conjunction with the accompanying figures.

DETAILED DESCRIPTION

[0058] A detailed description of one or more embodiments of the invention is provided below. The invention is described in connection with such embodiments, but the invention is not limited to any particular embodiment described herein. The scope of the invention is limited only by the claims and equivalents thereof. Numerous specific details are set forth in the following description in order to provide a thorough understanding of the invention. These details are provided for the purpose of providing non-limiting examples and the invention may be practiced according to the claims without some or all of these specific details.

Definitions

[0059] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by a person of ordinary skill in the art to which the present invention pertains. As used herein, and unless stated otherwise or required otherwise by context, each of the following terms shall have the definition set forth below.

[0060] Articles such as “a” and “an” when used in a claim, are understood to mean one or more of what is claimed or described.

[0061] The term “pancreatic cancer-negative” with reference to a sample, generally refers to a biological sample from an individual that does not suffer from pancreatic cancer or is not predisposed to developing pancreatic cancer.

[0062] The term “baseline” or “control” generally refers to a value corresponding to a concentration of a protein or peptide fragment thereof in an individual that does not suffer from pancreatic cancer or is not predisposed to developing pancreatic cancer or a value derived from a population of such individuals and/or from published data.

[0063] The term “pancreatic cancer treatment regime” generally refers to an intervention made in response to a subject suffering from pancreatic cancer. The aim of the regime may include, but is not limited to, one or more of the alleviation or prevention of symptoms, slowing or stopping the progression or worsening of pancreatic cancer and causing the remission of pancreatic cancer.

[0064] In some embodiments, “pancreatic cancer treatment regime” refers to therapeutic treatment (e.g., changing pancreatic cancer-related proteomic levels) by one or more suitable therapeutic agents administered to a patient, such as chemotherapeutic agents.

[0065] The terms “comprises”, “comprising”, “include”, “includes”, “including”, “contain”, “contains” and “containing” are meant to be non-limiting, i.e., other steps and other sections which do not affect the end of result can be added. The above terms encompass the terms “consisting of and “consisting essentially of .

[0066] The term “pancreatic cancer-related proteome” or “proteomic profile” generally refers to a profile of proteins associated with pancreatic cancer comprising a plurality of proteins comprising at least one of apolipoprotein Al, apolipoprotein A-II, plasma protease Cl inhibitor, L-selectin, tetranectin, phospholipid transfer protein, apolipoprotein M, gelsolin, adipocyte plasma membrane-associated protein, Cis complement factor, C4b complement factor, C6 complement factor and fibronectin or a combination thereof.

[0067] The phrase “reference value derived therefrom” in connection with comparing the level of a protein in a sample with a reference refers to a value that is derived from a sample or from a plurality of subjects that do not have pancreatic cancer. For example, the reference value may be derived from statistical data previously collected from subjects that do not have pancreatic cancer.

[0068] The terms “preventing” and “prevention” are used interchangeably and generally refer to any activity that leads to a reduction in risk of developing pancreatic cancer in the subject. [0069] The term “subject” generally refers to a vertebrate, such as a mammal. The term “mammal” is defined as individual belonging to the class Mammalia. In some embodiments, the subject is human.

[0070] The term “treating”, or “treatment” generally refers to an intervention made in response to pancreatic cancer or associated symptoms thereof. The aim of treatment may include, but is not limited to, one or more of the alleviation or prevention of pancreatic cancer, slowing or stopping the progression or worsening of pancreatic cancer and the remission of pancreatic cancer. In certain embodiments, “treatment” refers to surgery and/or administration of a therapeutic agent for treatment of pancreatic cancer. Such treatment may further comprise radiation treatment.

[0071] The term “pancreatic cancer drug” refers to any therapeutic agent or prodrug used to treat or reduce progression of pancreatic cancer. The drug may be included in a pharmaceutical formulation and optionally comprises excipients.

[0072] The term “biopsy” as used herein with reference to determining if a subject has pancreatic cancer, refers to a composition comprising cells and/or fluids, without limitation, from one or more of the duodenum, bile ducts, pancreas and/or pancreatic duct of the subject.

[0073] The term “preferred” or “preferably” refers to a non-limiting example of the disclosure and should not be construed as limiting.

[0074] The term “computer-implemented” with reference to a method or process means that all or a significant portion of the steps of the method are carried out by an electronic data processor and/or by distributed computing, such as cloud computing.

[0075] In all embodiments of the present disclosure, all percentages, concentrations, parts and ratios are based upon the total weight of the compositions of the present disclosure, unless otherwise specified. All such weights as they pertain to listed ingredients are based on the active level and, therefore do not include solvents or by-products that may be included in commercially available materials, unless otherwise specified.

Modelling data [0076] In one embodiment, between 1 and 50, 2 and 40 or 5 and 30 biomarkers are assessed as based on pancreatic cancer modelling data. Such data is used to assess whether a given biomarker is predictive of pancreatic cancer.

[0077] In one embodiment, the modelling data is obtained from a pancreatic cancer test and control group data, each group data subjected to a computer-implemented calculation comprising at least one of: a computer-generated Receiver Operating Characteristic (ROC) curve analysis, a Principal Component Analysis (PCA) plot, and a latent structures discriminant analysis (PLS-DA) model and/or a Variable Importance of Projection (VIP) plot and thereby obtaining a set of at least 2, 3, 4, 5, 6, 7, 8, 9, 10 or more biomarkers identified as contributing to the diagnosis, development or regression of pancreatic cancer relative to other biomarkers measured. In some embodiments, the disclosure is based on identifying a subject as having a risk of having pancreatic cancer by determining whether a biological sample from the patient has elevated or reduced levels of a novel combination of proteins or fragments thereof identified by the inventors as being predictive of the presence of pancreatic cancer. The identified subject is then subjected to one or more steps comprising obtaining a biopsy (e.g., cells and/or fluids from the duodenum, bile duct(s), pancreas and/or pancreatic duct) and analyzing the biopsy for the presence of cancerous cells.

[0078] In some embodiments, the biomarkers are previously selected from proteomic profiles obtained from computer modelling. In some non -limiting examples, at least 2, 3, 4, or 5 proteomic biomarkers are measured. In further embodiments, up to 100, 95, 90, 85, 80, 75, 70, 65, 60, 55, 50, 45, 40, 35, 30, 25 or 20 proteomic biomarkers are identified based on the computer modelling. Optionally, this includes selecting metabolomic biomarkers in addition to proteomic biomarkers.

[0079] In some embodiments, the biomarkers are selected from computer modelling based on assigning a weight to biomarkers in a proteomic profile, and optionally further based on a metabolic profile, the weight based on the ability of the marker to diagnose and/or assess pancreatic cancer progression. Method of Diagnosing and Treating Pancreatic Cancer

[0080] In one aspect, the present disclosure relates to methods for (e.g., early) diagnosis and treatment of pancreatic cancer, and any associated symptoms, in a subject. The disclosure in some embodiments provides, at least in part, the identification of proteins or peptide fragments thereof that provide etiological data related to pancreatic cancer and provides an opportunity for objective protein-based or peptide-based diagnosis of pancreatic cancer that can lead to more effective therapy. Given the complexities of the interactions between genetics and the environment, proteomic profiling, optionally in combination with other profiling (e.g., genomic and/or metabolomic profiling), can provide an approach towards a better understanding of pancreatic cancer and the development of diagnostic tests that aid in individualized treatment decisions. In one embodiment, the method comprises a proteomic analysis within a multi-omic analysis, which includes a proteomic and a genomic and/or metabolomic analysis. Multi-omic based analysis has the advantage to identify biomarker profiles derived from an individual’s inherited genes as well as capture the interactions of the individual’s current lifestyle behaviors (e.g., smoking, alcohol consumption, sleep behaviours, physical activity and the like), gut microbiome, dietary, and environmental factors that contribute to the unique protein profile of a subject with pancreatic cancer. Combining early diagnoses and a pancreatic cancer treatment regime has the further advantage of increased positive therapeutic outcomes. Described herein are methods that provide for the identification of new proteomic profiles among subjects with pancreatic cancer that serve to diagnose and treat those subjects. Therefore, the present disclosure provides an advancement in the art.

[0081] With the present disclosure, a new proteomic profile for pancreatic cancer is identified in a subject having pancreatic cancer. The proteomic profile for pancreatic cancer comprises at least one, at least two, at least three, at least four, at least five, at least six or at least seven pancreatic cancer-related proteins selected from apolipoprotein Al, apolipoprotein A-II, plasma protease Cl inhibitor, L-selectin, tetranectin, phospholipid transfer protein, apolipoprotein M, gelsolin, adipocyte plasma membrane-associated protein, Cis complement factor, C4b complement factor or C6 complement factor and fibronectin.

[0082] The protein, apolipoprotein Al is identified herein as a biomarker of pancreatic cancer and in some embodiments is elevated to a level of about 1.2 to 10 times or greater compared to a median level of a reference apolipoprotein Al in pancreatic cancer-negative individuals. In some embodiments, an elevated level of apolipoprotein Al of 1.2 times or more identifies the subject as having pancreatic cancer, such as stage 1 or 2 pancreatic cancer. Apolipoprotein Al is currently believed to be a tumor suppressor. Apolipoprotein Al (ApoAl) is a protein involved in lipid metabolism and has been studied for its potential role in pancreatic cancer.

[0083] Alternatively or additionally, the protein, apolipoprotein A-II is identified herein as a biomarker of pancreatic cancer and in some embodiments is elevated to a level of about 1.2 to 10 times or greater compared to a median level of a reference apolipoprotein A-II in pancreatic cancer-negative individuals. In some embodiments, an elevated level of apolipoprotein A-II of 1.2 times or more identifies the subject as having pancreatic cancer, such as stage 1 or 2 pancreatic cancer.

[0084] Alternatively or additionally, the protein, plasma protease Cl inhibitor may be measured as a biomarker of pancreatic cancer. The plasma protease Cl inhibitor may be elevated to a level of about 1.2 to 10 times or greater compared to a median level of a reference plasma protease Cl inhibitor in pancreatic cancer-negative individuals. In some embodiments, an elevated level of plasma protease Cl inhibitor of 1.2 times or more identifies the subject as having pancreatic cancer, such as stage 1 or 2 pancreatic cancer. Plasma protease inhibitor 1 (Cl inhibitor) is a protein involved in the regulation of the complement system, which is a component of the immune system.

[0085] Alternatively or additionally, the protein, L-selectin may be measured as a biomarker of pancreatic cancer. L-selectin is a cell adhesion molecule that is expressed on the surface of immune cells and is involved in the migration of these cells to sites of inflammation.

[0086] In some embodiments L-selectin is elevated to a level of about 1.2 to 10 times or greater compared to a median level of a reference L-selectin in pancreatic cancer-negative individuals. In some embodiments, an elevated level of L-selectin of 1.2 times or more identifies the subject as having pancreatic cancer, such as stage 1 or 2 pancreatic cancer.

[0087] Alternatively or additionally, the protein, tetranectin may be measured as a biomarker of pancreatic cancer. Tetranectin, also known as plasminogen activator inhibitor-tissue factor pathway inhibitor-2, is a protein involved in blood coagulation and has also been shown to have anti-tumor properties. Tetranectin is produced by various cell types in the body, including endothelial cells, platelets, and monocytes. It is also found in various tissues, including the liver, lung, and placenta. In some embodiments tetranectin elevated to a level of about 1.2 to 10 times or greater compared to a median level of a reference tetranectin in pancreatic cancer-negative individuals. In some embodiments, an elevated level of tetranectin of 1.2 times or more identifies the subject as having pancreatic cancer, such as stage 1 or 2 pancreatic cancer.

[0088] Alternatively or additionally, the protein, phospholipid transfer protein may be measured as a biomarker of pancreatic cancer. In some embodiments phospholipid transfer protein is elevated to a level of about 1.2 to 10 times or greater compared to a median level of a reference phospholipid transfer protein in pancreatic cancer-negative individuals. In some embodiments, an elevated level of phospholipid transfer protein of 1.2 times or more identifies the subject as having pancreatic cancer, such as stage 1 or 2 pancreatic cancer.

[0089] Alternatively or additionally, the protein, Apolipoprotein M may be measured as a biomarker of pancreatic cancer and in some embodiments is elevated to a level of about 1.2 to 10 times or greater compared to a median level of a reference Apolipoprotein M in pancreatic cancernegative individuals. In some embodiments, an elevated level of Apolipoprotein M of 1.2 times or more identifies the subject as having pancreatic cancer, such as stage 1 or 2 pancreatic cancer.

[0090] Alternatively or additionally, Cis complement factor may be measured as a biomarker of pancreatic cancer and in some embodiments is elevated to a level of about 1.2 to 10 times or greater compared to a median level of a reference Cis complement factor in pancreatic cancer-negative individuals. In some embodiments, an elevated level of Cis complement factor of 1.2 times or more identifies the subject as having pancreatic cancer, such as stage 1 or 2 pancreatic cancer.

[0091] Alternatively or additionally, C4b complement factor may be measured as a biomarker of pancreatic cancer and in some embodiments is elevated to a level of about 1.2 to 10 times or greater compared to a median level of a reference C4b complement factor in pancreatic cancer-negative individuals. In some embodiments, an elevated level of C4b complement factor of 1.2 times or more identifies the subject as having pancreatic cancer, such as stage 1 or 2 pancreatic cancer. [0092] Alternatively or additionally, C6 complement factor may be measured as a biomarker of pancreatic cancer and in some embodiments is elevated to a level of about 1.2 to 10 times or greater compared to a median level of a reference C6 complement factor in pancreatic cancer-negative individuals. In some embodiments, an elevated level of C6 complement factor of 1.2 times or more identifies the subject as having pancreatic cancer, such as stage 1 or 2 pancreatic cancer.

[0093] Alternatively or additionally, the protein, gelsolin may be measured as a biomarker of pancreatic cancer. Gelsolin has established roles in cell motility and in some embodiments is elevated to a level of about 1.2 to 10 times or greater compared to a median level of a reference gelsolin in pancreatic cancer-negative individuals. In some embodiments, an elevated level of gelsolin of 1.2 times or more identifies the subject as having pancreatic cancer, such as stage 1 or 2 pancreatic cancer.

[0094] Alternatively or additionally, the protein, adipocyte plasma membrane-associated protein may be measured as a biomarker of pancreatic cancer. Adipocyte plasma membrane-associated protein, also known as adipophilin, is a protein that is expressed in lipid droplets, which are cellular organelles that store lipids such as fats. Adipophilin is expressed in adipose (fat) tissue, and thus, weight loss can lead to a decrease in its levels in the blood. Regular physical activity has been shown to reduce adipose tissue and thus, lower adipophilin levels in the blood. Consuming a diet that is low in fat and high in fiber, fruits, and vegetables may help to reduce adipophilin levels in the blood. Certain medications, such as statins, which are used to lower cholesterol levels, have been shown to reduce adipophilin levels in the blood, and in some embodiments is elevated to a level of about 1.2 to 10 times or greater compared to a median level of a reference adipocyte plasma membrane-associated protein in pancreatic cancer-negative individuals. In some embodiments, an elevated level of adipocyte plasma membrane-associated protein of 1.2 times or more identifies the subject as having pancreatic cancer, such as stage 1 or 2 pancreatic cancer.

[0095] Alternatively or additionally, the protein fibronectin may be measured as a biomarker of pancreatic cancer and in some embodiments is elevated to a level of about 1.2 to 10 times or greater compared to a median level of a reference fibronectin in pancreatic cancer-negative individuals. In some embodiments, an elevated level of fibronectin of 1.2 times or more identifies the subject as having pancreatic cancer, such as stage 1 or 2 pancreatic cancer. [0096] In one aspect, the present disclosure provides for a method of diagnosing and treating pancreatic cancer in a subject. The method comprises step (a) providing a biological sample obtained from the subject, such as a human. In accordance with the methods disclosed herein, any type of biological sample that originates anywhere from the body of a subject may be tested, including but not limited to, blood (including, but not limited to serum or plasma), cerebrospinal fluid (“CSF”), pleural fluid, urine, stool, sweat, tears, breath condensate, saliva vitreous humour, a tissue sample, amniotic fluid, a chorionic villus sampling, brain tissue, a biopsy of any solid tissue including tumor, adjacent normal, smooth and skeletal muscle, adipose tissue, liver, skin, hair, brain, kidney, pancreas, lung or the like may be used. In one embodiment, the biological sample is obtained from blood. The pancreatic cancer-related proteins may be extracted from the biological source using any number of extraction/purification procedures that are typically used in quantitative analytical chemistry.

[0097] The method further comprises step (b), which includes measuring concentration levels of at least one, at least two, at least three, at least four, at least five, at least six or at least seven pancreatic cancer-related proteins or peptide fragments thereof selected from the group consisting of apolipoprotein Al, apolipoprotein A-II, plasma protease Cl inhibitor, L-selectin, tetranectin, phospholipid transfer protein, apolipoprotein M, gelsolin, adipocyte plasma membrane-associated protein, Cis complement factor, C4b complement factor, C6 complement factor and fibronectin from the obtained sample. In certain embodiments, the method comprises measuring at least 8, 9, 10, 11, 12, 13, 14 or 15 pancreatic cancer-related proteins or fragments thereof from the obtained sample.

[0098] In certain embodiments, the method may further include measuring the concentration levels of one or more additional pancreatic cancer-related proteins or peptide fragments thereof in addition to the foregoing proteins, including, but not limited to, any of those known in the art. Such markers include carbohydrate antigen 19-9 (CA 19-9) (See Goonetilleke and Siriwardena, 2007, Eur J Surg Oncol. 33(3): 266-70, which is incorporated herein by reference), CA 242, hCG beta, CA 72-4 and carcinoembryonic antigen (CEA) (See Louhimo et al., 2004, Oncology, 66(2): 125-31, which is incorporated herein by reference). [0099] The method described herein further comprises step (c) comparing the concentration levels of the pancreatic cancer-related proteins or peptide fragments thereof from the obtained sample to the concentration levels of reference pancreatic cancer-related proteins or peptide fragments thereof from a pancreatic cancer-negative sample(s) or a reference value derived therefrom. One skilled in the art will appreciate that references can be established as a value representative of the level of pancreatic cancer-related proteins or peptide fragments thereof in a population that do not have pancreatic cancer for the comparison. Various criteria may be used to determine the inclusion and/or exclusion of a particular subject in the reference population, including age of the subject (e.g., the reference subject can be within the same age group as the subject in need of treatment) and gender of the subject (e.g., the reference subject can be the same gender as the subject in need of treatment). In certain embodiments, the reference is from a pancreatic cancer-negative sample or an average of a number of samples. In another example, the concentration levels of the reference pancreatic cancer-related proteins or peptide fragments thereof are derived from patient populations.

[00100] The method described herein further comprises step (d) identifying the subject as having pancreatic cancer if the concentration levels of the pancreatic cancer-related proteins or peptide fragments thereof from the obtained sample are different relative to the concentration levels of the reference pancreatic cancer-related proteins or peptide fragments thereof from the pancreatic cancer-negative sample(s) or a reference value derived therefrom. In certain embodiments, the identifying step (d) occurs upon determination that the concentration level of the at least one pancreatic cancer-related proteins or peptide fragments thereof from the obtained sample differs by about 10% or more, 20% or more, about 30% or more, about 40% or more, about 50% or more, about 60% or more, or about 70% or more relative to the concentration level of the at least one reference pancreatic cancer-related protein from the pancreatic cancer-negative sample(s) or a reference value derived therefrom. In certain embodiments, the identifying step (d) occurs upon determination that the concentration levels of at least two, at least three, at least four, at least five, at least six or at least seven pancreatic cancer-related proteins or peptide fragments thereof from the obtained sample differ by about 20% or more, about 30% or more, about 40% or more, about 50% or more, about 60% or more, or about 70% or more relative to the concentration levels of the reference pancreatic cancer-related proteins or fragments from the pancreatic cancer-negative sample(s) or a reference value derived therefrom. [00101] In certain embodiments, the identifying step (d) occurs upon determination that the concentration levels of at least the apolipoprotein Al from the obtained sample are decreased relative to the concentration levels of the reference apolipoprotein Al from the pancreatic cancernegative sample(s) or a reference value derived therefrom. In some aspects, the concentration level of the apolipoprotein Al level from the obtained sample is higher than about 20% or more, about 30% or more, about 40% or more, about 50% or more, about 60% or more, or about 70% or more relative to the concentration level of the reference apolipoprotein Al obtained or derived from the pancreatic cancer-negative sample(s) or a reference value derived therefrom. In some aspects, the concentration level of the apolipoprotein Al level from the obtained sample is lower than about 20% or more, about 30% or more, about 40% or more, about 50% or more, about 60% or more, or about 70% or more relative to the concentration level of the reference apolipoprotein Al from the pancreatic cancer-negative sample(s) or a reference value derived therefrom.

[00102] In certain embodiments, the identifying step (d) occurs upon determination that the concentration levels of at least the apolipoprotein A-II from the obtained sample are decreased relative to the concentration levels of the reference apolipoprotein A-II from the pancreatic cancernegative sample(s) or a reference value derived therefrom. In some aspects, the concentration level of the apolipoprotein A-II level from the obtained sample is higher than about 20% or more, about 30% or more, about 40% or more, about 50% or more, about 60% or more, or about 70% or more relative to the concentration level of the reference apolipoprotein A-II from the pancreatic cancernegative sample(s) or a reference value derived therefrom. In some aspects, the concentration level of the apolipoprotein A-II level from the obtained sample is lower than about 20% or more, about 30% or more, about 40% or more, about 50% or more, about 60% or more, or about 70% or more relative to the concentration level of the reference apolipoprotein A-II from the pancreatic cancernegative sample(s) or a reference value derived therefrom.

[00103] In certain embodiments, the identifying step (d) occurs upon determination that the concentration levels of at least the plasma protease Cl inhibitor from the obtained sample are decreased relative to the concentration levels of the reference plasma protease Cl inhibitor from the pancreatic cancer-negative sample(s) or a reference value derived therefrom. In some aspects, the concentration level of the plasma protease C 1 inhibitor level from the obtained sample is higher than about 20% or more, about 30% or more, about 40% or more, about 50% or more, about 60% or more, or about 70% or more relative to the concentration level of the reference plasma protease Cl inhibitor from the pancreatic cancer-negative sample(s) or a reference value derived therefrom. In some aspects, the concentration level of the plasma protease Cl inhibitor level from the obtained sample is lower than about 20% or more, about 30% or more, about 40% or more, about 50% or more, about 60% or more, or about 70% or more relative to the concentration level of the reference plasma protease Cl inhibitor from the pancreatic cancer- negative sample(s) or a reference value derived therefrom.

[00104] In certain embodiments, the identifying step (d) occurs upon determination that the concentration levels of at least the L-selectin from the obtained sample are decreased relative to the concentration levels of the reference L-selectin from the pancreatic cancer-negative sample. In some aspects, the concentration level of the L-selectin level from the obtained sample is higher than about 20% or more, about 30% or more, about 40% or more, about 50% or more, about 60% or more, or about 70% or more relative to the concentration level of the reference L-selectin from the pancreatic cancer-negative sample. In some aspects, the concentration level of the L-selectin level from the obtained sample is lower than about 20% or more, about 30% or more, about 40% or more, about 50% or more, about 60% or more, or about 70% or more relative to the concentration level of the reference L-selectin from the pancreatic cancer- negative sample.

[00105] In certain embodiments, the identifying step (d) occurs upon determination that the concentration levels of at least the tetranectin from the obtained sample are decreased relative to the concentration levels of the reference tetranectin from the pancreatic cancer-negative sample. In some aspects, the concentration level of the tetranectin level from the obtained sample is higher than about 20% or more, about 30% or more, about 40% or more, about 50% or more, about 60% or more, or about 70% or more relative to the concentration level of the reference tetranectin from the pancreatic cancer-negative sample. In some aspects, the concentration level of the tetranectin level from the obtained sample is lower than about 20% or more, about 30% or more, about 40% or more, about 50% or more, about 60% or more, or about 70% or more relative to the concentration level of the reference tetranectin from the pancreatic cancer- negative sample.

[00106] In certain embodiments, the identifying step (d) occurs upon determination that the concentration levels of at least the phospholipid transfer protein from the obtained sample are decreased relative to the concentration levels of the reference phospholipid transfer protein from the pancreatic cancer-negative sample. In some aspects, the concentration level of the phospholipid transfer protein level from the obtained sample is higher than about 20% or more, about 30% or more, about 40% or more, about 50% or more, about 60% or more, or about 70% or more relative to the concentration level of the reference phospholipid transfer protein from the pancreatic cancernegative sample. In some aspects, the concentration level of the phospholipid transfer protein level from the obtained sample is lower than about 20% or more, about 30% or more, about 40% or more, about 50% or more, about 60% or more, or about 70% or more relative to the concentration level of the reference phospholipid transfer protein from the pancreatic cancer- negative sample.

[00107] In certain embodiments, the identifying step (d) occurs upon determination that the concentration levels of at least the apolipoprotein M from the obtained sample are decreased relative to the concentration levels of the reference apolipoprotein M from the pancreatic cancernegative sample. In some aspects, the concentration level of the apolipoprotein M level from the obtained sample is higher than about 20% or more, about 30% or more, about 40% or more, about 50% or more, about 60% or more, or about 70% or more relative to the concentration level of the reference apolipoprotein M from the pancreatic cancer-negative sample. In some aspects, the concentration level of the apolipoprotein M level from the obtained sample is lower than about 20% or more, about 30% or more, about 40% or more, about 50% or more, about 60% or more, or about 70% or more relative to the concentration level of the reference apolipoprotein M from the pancreatic cancer- negative sample.

[00108] In certain embodiments, the identifying step (d) occurs upon determination that the concentration levels of at least the gelsolin from the obtained sample are decreased relative to the concentration levels of the reference gelsolin from the pancreatic cancer-negative sample. In some aspects, the concentration level of the gelsolin level from the obtained sample is higher than about 20% or more, about 30% or more, about 40% or more, about 50% or more, about 60% or more, or about 70% or more relative to the concentration level of the reference gelsolin from the pancreatic cancer-negative sample. In some aspects, the concentration level of the gelsolin level from the obtained sample is lower than about 20% or more, about 30% or more, about 40% or more, about 50% or more, about 60% or more, or about 70% or more relative to the concentration level of the reference gelsolin from the pancreatic cancer- negative sample. [00109] In certain embodiments, the identifying step (d) occurs upon determination that the concentration levels of at least the adipocyte plasma membrane-associated protein from the obtained sample are decreased relative to the concentration levels of the reference adipocyte plasma membrane-associated protein from the pancreatic cancer-negative sample. In some aspects, the concentration level of the adipocyte plasma membrane-associated protein level from the obtained sample is higher than about 20% or more, about 30% or more, about 40% or more, about 50% or more, about 60% or more, or about 70% or more relative to the concentration level of the reference adipocyte plasma membrane-associated protein from the pancreatic cancer-negative sample. In some aspects, the concentration level of the adipocyte plasma membrane-associated protein level from the obtained sample is lower than about 20% or more, about 30% or more, about 40% or more, about 50% or more, about 60% or more, or about 70% or more relative to the concentration level of the reference adipocyte plasma membrane-associated protein from the pancreatic cancer- negative sample.

[00110] In certain embodiments, the identifying step (d) occurs upon determination that the concentration levels of at least the Cis complement factor from the obtained sample are decreased relative to the concentration levels of the reference Cis complement factor from the pancreatic cancer-negative sample. In some aspects, the concentration level of the Cis complement factor level from the obtained sample is higher than about 20% or more, about 30% or more, about 40% or more, about 50% or more, about 60% or more, or about 70% or more relative to the concentration level of the reference Cis complement factor from the pancreatic cancer-negative sample. In some aspects, the concentration level of the Cis complement factor level from the obtained sample is lower than about 20% or more, about 30% or more, about 40% or more, about 50% or more, about 60% or more, or about 70% or more relative to the concentration level of the reference Cis complement factor from the pancreatic cancer- negative sample.

[00111] In certain embodiments, the identifying step (d) occurs upon determination that the concentration levels of at least the C4b complement factor from the obtained sample are decreased relative to the concentration levels of the reference C4b complement factor from the pancreatic cancer-negative sample. In some aspects, the concentration level of the C4b complement factor level from the obtained sample is higher than about 20% or more, about 30% or more, about 40% or more, about 50% or more, about 60% or more, or about 70% or more relative to the concentration level of the reference C4b complement factor from the pancreatic cancer-negative sample. In some aspects, the concentration level of the C4b complement factor level from the obtained sample is lower than about 20% or more, about 30% or more, about 40% or more, about 50% or more, about 60% or more, or about 70% or more relative to the concentration level of the reference C4b complement factor from the pancreatic cancer-negative sample.

[00112] In certain embodiments, the identifying step (d) occurs upon determination that the concentration levels of at least the C6 complement factor from the obtained sample are decreased relative to the concentration levels of the reference C6 complement factor from the pancreatic cancer-negative sample. In some aspects, the concentration level of the C6 complement factor level from the obtained sample is higher than about 20% or more, about 30% or more, about 40% or more, about 50% or more, about 60% or more, or about 70% or more relative to the concentration level of the reference C6 complement factor from the pancreatic cancer-negative sample. In some aspects, the concentration level of the C6 complement factor level from the obtained sample is lower than about 20% or more, about 30% or more, about 40% or more, about 50% or more, about 60% or more, or about 70% or more relative to the concentration level of the reference C6 complement factor from the pancreatic cancer- negative sample.

[00113] In certain embodiments, the identifying step (d) occurs upon determination that the concentration levels of at least the fibronectin from the obtained sample are decreased relative to the concentration levels of the reference fibronectin from the pancreatic cancer-negative sample. In some aspects, the concentration level of the fibronectin level from the obtained sample is higher than about 20% or more, about 30% or more, about 40% or more, about 50% or more, about 60% or more, or about 70% or more relative to the concentration level of the reference fibronectin from the pancreatic cancer-negative sample. In some aspects, the concentration level of the fibronectin level from the obtained sample is lower than about 20% or more, about 30% or more, about 40% or more, about 50% or more, about 60% or more, or about 70% or more relative to the concentration level of the reference fibronectin from the pancreatic cancer- negative sample.

[00114] The method described herein further comprises step (e) treating the subject so identified as having pancreatic cancer with a pancreatic cancer treatment regime. [00115] In certain embodiments of any of the methods described herein, the comparison of the concentration level of the at least one pancreatic cancer-related protein from the obtained sample, or a value derived therefrom, to the concentration level of the reference pancreatic cancer-related protein from the pancreatic cancer-negative sample comprises using multivariate statistical analysis. In one embodiment, the multivariate statistical analysis is selected from principal component analysis (“PC A”), or partial least squares projects to latent structures discriminant analysis (“PLS-DA”). In certain embodiments, a computer is used for statistical analysis. Data for statistical analysis can be extracted from chromatograms (i.e., spectra of mass signals) using software for statistical methods known in the art.

[00116] In some aspects, the present disclosure relates to a method of monitoring pancreatic cancer progression and treating the pancreatic cancer in a subject. In one embodiment, the method includes quantifying the pancreatic cancer-related proteins, or peptide fragments thereof, at one or more time points after the initiation of treatment to monitor pancreatic cancer progression or regression in a subject. Accordingly, the method comprises: (a) providing a first biological sample obtained from the subject at a first time; (b) assessing a first pancreatic cancer-related proteomic profile by measuring concentration levels of at least one, at least two, at least three, at least four, at least five, at least six or at least seven pancreatic cancer-related proteins or peptide fragments thereof selected from apolipoprotein Al, apolipoprotein A-II, plasma protease Cl inhibitor, L- selectin, tetranectin, phospholipid transfer protein, apolipoprotein M, gelsolin, adipocyte plasma membrane-associated protein, Cis complement factor, C4b complement factor, C6 complement factor and fibronectinfrom the first obtained sample; (c) comparing the first pancreatic cancer- related proteomic profile with a reference pancreatic cancer-related proteomic profile from a pancreatic cancer-negative sample; (d) determining that there is a first difference between the first pancreatic cancer-related proteomic profile and the reference pancreatic cancer-related proteomic profile from the pancreatic cancer-negative sample, the first difference being indicative of pancreatic cancer; (e) providing a second biological sample obtained from the subject at a second time that is after the first time; (f) assessing a second pancreatic cancer-related proteomic profile by measuring concentration levels of the pancreatic cancer-related proteins or peptide fragments thereof from the second obtained sample; (g) comparing the second pancreatic cancer-related proteomic profile with the reference pancreatic cancer-related proteomic profile from the pancreatic cancer-negative sample; (h) determining that there is a second difference between the first pancreatic cancer-related proteomic profile and the reference pancreatic cancer-related proteomic profile from the pancreatic cancer-negative sample, the second difference being indicative of pancreatic cancer; (i) determining pancreatic cancer progression or regression based at least in part on the first and second difference; and (j) treating the subject as identified with an pancreatic cancer treatment regime.

[00117] In certain embodiments of the above method, the period between the first time and the second time is at least 1 month, at least 2 months, at least 3 months, at least 6 months, at least 9 months, or at least 12 months, preferably at least 3 months. In some embodiments, the treatment has been administered to the subject before the first two biological samples have been obtained. In other embodiments, the treatment has been administered to the subject in the interval(s) between the taking of the biological samples. In certain embodiments, the first biological sample, the second biological sample, or both are blood or urine, preferably serum, plasma or urine.

[00118] The present disclosure also provides for a method for diagnosing and treating pancreatic cancer in a subject. The method comprises: (a) providing a biological sample obtained from the subject; (b) measuring concentration levels of at least one, at least two, at least three, at least four, at least five, at least six or at least seven pancreatic cancer-related proteins or protein fragments thereof, selected from the group consisting of apolipoprotein Al, apolipoprotein A-II, plasma protease Cl inhibitor, L-selectin, tetranectin, phospholipid transfer protein, apolipoprotein M, gelsolin, adipocyte plasma membrane-associated protein, Cis complement factor, C4b complement factor, C6 complement factor and fibronectin; (c) comparing the concentration levels of the pancreatic cancer-related proteins or peptide fragments thereof from the obtained sample to the concentration levels of reference pancreatic cancer-related proteins or fragments thereof from an pancreatic cancer-negative sample; (d) identifying the subject as having pancreatic cancer if the concentration levels of the pancreatic cancer-related proteins or fragments thereof from the obtained sample are different relative to the concentration levels of the reference pancreatic cancer- related proteins or fragments thereof from the pancreatic cancer-negative sample; and (e) treating the subject so identified with an pancreatic cancer treatment regime.

[00119] The present disclosure also provides for a method for diagnosing and treating pancreatic cancer in a subject that comprises: (a) providing a biological sample obtained from the subject; (b) measuring concentration levels of at least one, at least two, at least three, at least four, at least five, at least six or at least seven pancreatic cancer-related proteins or fragments thereof selected from the group consisting of apolipoprotein Al, apolipoprotein A-II, plasma protease Cl inhibitor, L- selectin, tetranectin, phospholipid transfer protein, apolipoprotein M, gelsolin, adipocyte plasma membrane-associated protein, Cis complement factor, C4b complement factor, C6 complement factor and fibronectin from the obtained sample; (c) comparing the concentration levels of the pancreatic cancer-related proteins or fragments thereof from the obtained sample to the concentration levels of reference pancreatic cancer-related proteins or fragments thereof from a pancreatic cancer-negative sample or baseline; (d) measuring concentration levels of at least one, at least two, at least three, at least four, at least five, at least six or at least seven pancreatic cancer- related proteins or fragments selected from the group consisting of apolipoprotein Al, apolipoprotein A-II, plasma protease Cl inhibitor, L-selectin, tetranectin, phospholipid transfer protein, apolipoprotein M, gelsolin, adipocyte plasma membrane-associated protein, Cis complement factor, C4b complement factor, C6 complement factor and fibronectin ; (e) comparing the concentration levels of the pancreatic cancer-related proteins or fragments thereof from the obtained sample to the concentration levels of reference pancreatic cancer-related proteins or fragments thereof from an pancreatic cancer- negative sample or baseline; (f) identifying the subject as having pancreatic cancer if the concentration levels of the pancreatic cancer- related proteins or fragments thereof from the obtained sample are different relative to the concentration levels of the reference pancreatic cancer-related proteins or fragments thereof from the pancreatic cancer-negative sample, and the concentration levels of the pancreatic cancer-related proteins or fragments thereof from the obtained sample are different relative to the concentration levels of the reference pancreatic cancer-related proteins or fragments thereof from the pancreatic cancernegative sample or baseline; and (g) treating the subject so identified with a pancreatic cancer treatment regime.

[00120] In certain embodiments of the above method, the identifying step (f) occurs upon determination that the concentration levels of at least one, at least two, at least three, at least four, at least five, at least six or at least seven of the pancreatic cancer-related proteins or fragments thereof from the obtained sample differ by about 20% or more, about 30% or more, about 40% or more, about 50% or more, about 60% or more or about 70% or more relative to the concentration levels of the reference pancreatic cancer-related proteins or fragments from the pancreatic cancernegative sample or baseline.

Methods for quantifying pancreatic cancer-related proteins or peptide fragments thereof

[00121] In one embodiment, the pancreatic cancer-related proteins or peptide fragments thereof are measured by a spectroscopic technique, the spectroscopic technique being selected from the group consisting of liquid chromatography, gas chromatography, liquid chromatography mass spectrometry, gas chromatography mass spectrometry, high performance liquid chromatography mass spectrometry, capillary electrophoresis mass spectrometry, nuclear magnetic resonance spectrometry (NMR), raman spectroscopy, and infrared spectroscopy.

[00122] In certain embodiments, the measurement of the concentration levels of the pancreatic cancer-related proteins or peptide fragments thereof may be performed by a method comprising mass spectrometry, including but not limited to gas chromatography mass spectrometry (GC-MS) GC and liquid chromatography mass spectrometry (e.g., LC-MS, LC-MS-MS, LC-MRM, LC- SIM, and LC-SRM). In certain embodiments, the mass spectrometry is a multiple reaction monitoring mass spectrometry, a parallel reaction monitoring mass spectrometry, a matrix-assisted laser desorption/ionization (MALDI) mass spectrometry or a data-independent acquisition mass spectrometry. In still another embodiment, the multiple reaction monitoring mass spectrometry is an immuno-multiple reaction monitoring mass spectrometry, an immuno-parallel reaction monitoring, an immuno-MALDI or an immuno-data independent acquisition mass spectrometry.

[00123] In one embodiment, the procedure comprising mass spectrometry includes introducing a protein sample into a mass spectrometry unit, which is subsequently fragmented inside the mass spectrometry unit and the masses of the fragments are recorded and provided for analysis.

[00124] In some embodiments, the mass spectrometry process for determining whether the pancreatic-related proteins are elevated comprises enzymatic or chemical digestion of the proteins or peptide fragments thereof of a sample obtained from a subject into peptide fragments. The peptide fragments are optionally separated and/or ionized and captured by mass spectrometry. The digestion may comprise a proteolytic digestion involving treating a preparation comprising the pancreatic cancer-related proteins with an acid, base, or an enzyme such as trypsin or other proteolytic enzyme. One embodiment comprises a shotgun proteomics quantification in which the whole proteins in a complex mixture, such as serum, urine, and cell lysates, are hydrolyzed or otherwise cut into peptides and followed by multidimensional HPLC-MS, which aims to generate a global profile of protein mixtures as genome “shotgun” sequencing.

[00125] Thus, according to one aspect of the disclosure, there is provided a method for determining whether pancreatic-related proteins, or peptide fragments thereof, are elevated in a sample obtained from a subject, the pancreatic-related proteins or peptide fragments thereof being selected from at least one of pancreatic cancer-related proteins, or peptide fragments thereof, comprising the apolipoprotein Al, apolipoprotein A-II, plasma protease Cl inhibitor, L-selectin, tetranectin, phospholipid transfer protein, apolipoprotein M, gelsolin, adipocyte plasma membrane-associated protein, Cis complement factor, C4b complement factor, C6 complement factor and fibronectin, the method comprising enzymatic or chemical digestion of the proteins or peptide fragments thereof of the sample obtained from a subject into peptide fragments to produce peptide fragments thereof; introducing a solution comprising the peptide fragments to a mass spectrometer, optionally after one or more treatments comprising liquid chromatography or other treatments, to quantify the peptide fragments; determining the concentration of peptide fragment(s) relative to a baselines, such as a standard(s) (e.g., peptide standards); and assessing whether the fragment(s) are elevated relative to the baseline or standard(s); identifying the subject as having pancreatic cancer or a being predisposed to developing same if one or more of the peptides are elevated relative to the baseline or standard; and treating or causing the treating of the subject with a pancreatic cancer treatment, optionally comprising a chemotherapeutic agent that is approved for use to treat pancreatic cancer.

[00126] The proteins or peptide fragment thereof may be fragmented inside the mass spectrometry unit and the masses of the fragments recorded and provided for analysis.

[00127] The baseline is a normal level of a protein or peptide derived from a subject or a population of subjects that do not have pancreatic cancer. The standard may comprise one or more of the pancreatic cancer-related proteins, or peptide fragments thereof, at concentrations that correspond to such normal levels. The standard may be a value derived from a sample or samples obtained previously from subjects without pancreatic cancer. The standard may comprise one or more of the apolipoprotein Al, apolipoprotein A-II, plasma protease Cl inhibitor, L-selectin, tetranectin, phospholipid transfer protein, apolipoprotein M, gelsolin, adipocyte plasma membrane-associated protein, Cis complement factor, C4b complement factor, C6 complement factor and fibronectin, or fragments thereof.

[00128] In another embodiment, there is provided a plurality of standards comprising one or more of the pancreatic cancer-related peptide fragments, at concentrations that correspond to normal levels. The standards may comprise any combination of peptide fragments derived from apolipoprotein Al, apolipoprotein A-II, plasma protease Cl inhibitor, L-selectin, tetranectin, phospholipid transfer protein, apolipoprotein M, gelsolin, adipocyte plasma membrane-associated protein, Cis complement factor, C4b complement factor, C6 complement factor and fibronectin.

Pancreatic cancer treatment

[00129] Prior to pancreatic cancer treatment, the subject will typically have a biopsy to confirm the presence of pancreatic cancer. The biopsy may be selected from percutaneous biopsy, endoscopic biopsy or a surgical biopsy. A percutaneous biopsy involves inserting a hollow needle through the skin and into the pancreas to remove a tumour sample. The procedure may be facilitated by imaging, such as ultrasound or CT scans. An endoscopic biopsy involves passing an endoscope to the pancreas via the throat and small intestine. Samples are obtained from the bile or pancreatic ducts using an endoscopic ultrasound to pass a needle into the tumour or a brush is used to remove cells from the bile or pancreatic ducts. A surgical biopsy may be performed if it is desirable to determine whether the pancreatic cancer has spread. A surgical biopsy may be performed using laparoscopy (keyhole surgery). Optionally, additional tests are performed to assess if cancer cells obtained from the biopsy have mutations in certain genes. If mutations in genes implicated in pancreatic cancer are found, targeted therapy may be part of the pancreatic treatment regime. The data from the proteomic profile assessment may be used in conjunction with this information.

[00130] Imaging tests may be performed to facilitate diagnosis. Imaging tests may use x-rays, magnetic fields, sound waves, or radioactive substances to visualize a tumour. Examples of imaging include computer tomography (CT) scan, magnetic resonance imaging, ultrasound, cholangiopancreatography, such as magnetic resonance cholangiopancreatography or percutaneous transhepatic cholangiography, positron emission tomography scan or angiography.

[00131] The pancreatic treatment regime may include surgery to remove a tumour.

[00132] The pancreatic cancer treatment regime may alternatively or additionally include one or more therapeutic agents to treat pancreatic cancer. Examples of such therapeutic agents include the following: Abraxane (Paclitaxel Albumin-stabilized Nanoparticle Formulation); Afinitor (Everolimus); Capecitabine; Erlotinib Hydrochloride; Everolimus; 5-FU (Fluorouracil Injection); Fluorouracil; Gemcitabine, MRTX1133, which targets Kras G12D mutants, and/or Olaparib. The pancreatic cancer treatment may additionally or alternatively include radiation treatment to reduce tumour size.

[00133] In one embodiment, the one or more therapeutics are formulated in a delivery vehicle, such as a lipid nanoparticle. Therapeutics that are formulated into a delivery vehicle, such as a lipid nanoparticle, may include one or more RNA sequences of the pancreatic cancer biomarkers mentioned above or the RNA sequences of biomarkers associated with the aforementioned pancreatic biomarkers, which may be used to suppress their disease action or reduce their levels.

Kits

[00134] The proteomic profile described herein may be utilized in tests, assays, methods, kits for diagnosing, predicting, modulating or monitoring pancreatic cancer, including ongoing assessment, monitoring and/or susceptibility assessment. The present disclosure includes a kit for diagnosis of pancreatic cancer by measuring and identifying at least one or more pancreatic cancer- related proteins or fragments thereof associated with pancreatic cancer. Accordingly, the kit may comprise (a) a detector configured to detect concentration levels of at least one, at least two, at least three, at least four, at least five, at least six or at least seven pancreatic cancer-related proteins or fragments thereof selected from the group consisting of apolipoprotein Al, apolipoprotein A- II, plasma protease Cl inhibitor, L-selectin, tetranectin, phospholipid transfer protein, apolipoprotein M, gelsolin, adipocyte plasma membrane-associated protein, Cis complement factor, C4b complement factor, C6 complement factor and fibronectin in control levels corresponding to control group of pancreatic cancer-negative subjects, (c) a multivariate analysis system configured to analyze a difference in the concentration levels of the pancreatic cancer- related proteins or fragments thereof and the control levels, and (d) optionally, instructions for an pancreatic cancer diagnosis method, wherein the method comprises measuring, using the detector, the levels of the pancreatic cancer-related proteins or peptide fragments thereof from the obtained biological sample, and comparing the levels of the obtained pancreatic cancer-related proteins or peptides thereof to the control levels of the pancreatic cancer-related proteins or peptides thereof obtained from pancreatic cancer-negative subjects. In one embodiment, the pancreatic cancer diagnosis method comprises a multi-metabolite detector configured to measure the levels of pancreatic cancer- related proteins or peptides thereof. The detector may be part of a mass spectrometry unit, optionally operably communicating with a chromotography unit, such as a liquid chromatography unit.

[00135] In some aspects, the kit may be for the measurement of the pancreatic cancer-related proteins or fragments thereof by a physical separation technique (as described herein above). In some aspects, the kit may be for measurement of the pancreatic cancer-related proteins or peptides by a methodology other than a physical separation method, such as for non-limiting example, a colorimetric, enzymatic, and immunological methodology. The kit may also include one or more appropriate negative and/or positive controls. Kit of the present disclosure may include other reagents such as buffers and solutions for performing the tests.

Computer-Implemented Method

[00136] The disclosure is also directed to a computer-implemented method for processing a biological sample of a subject, diagnosing pancreatic cancer and treating the pancreatic cancer. The computer-implemented method may further allow monitoring of pancreatic cancer progression across multiple time points to support a more effective treatment regime.

[00137] The computer-implemented method comprises receiving a biological sample from the subject; processing the sample in a spectroscopy unit directly or wirelessly linked, or may utilize any suitable communication technology, to a processing device, the processing device having memory for storing measurement data from the spectroscopy unit; and in the spectroscopy unit, measuring levels of least one, at least two, at least three, at least four, at least five pancreatic, at least six or at least seven cancer-related proteins or fragments thereof selected from the group consisting of apolipoprotein Al, apolipoprotein A-II, plasma protease Cl inhibitor, L-selectin, tetranectin, phospholipid transfer protein, apolipoprotein M, gelsolin, adipocyte plasma membrane-associated protein, Cis complement factor, C4b complement factor, C6 complement factor and fibronectin and storing the measurement data in the processor. The processing device comprises one or more data storage devices that may be configured or adapted to store data related to the method. For example, the data storage device may be configured or adapted to store measurement data from the spectroscopy unit. The data storage device may also comprise computer program code stored thereon. The program code of this embodiment may include program code for at least performing the steps of the method aspect upon execution thereof.

[00138] The computer-implemented method further comprises comparing the stored measurement data to a value in the memory representing an pancreatic cancer-negative sample using multivariate statistical analysis; storing in the processing device a result corresponding to at least one, at least two, at least three, at least four, at least five, at least six or at least seven pancreatic cancer-related proteins or fragments thereof selected from the group consisting of apolipoprotein Al, apolipoprotein A-II, plasma protease Cl inhibitor, L-selectin, tetranectin, phospholipid transfer protein, apolipoprotein M, gelsolin, adipocyte plasma membrane-associated protein, Cis complement factor, C4b complement factor, C6 complement factor and fibronectin from the obtained sample, wherein the result identifies the subject as having pancreatic cancer if the measurement data representing the level of the pancreatic cancer-related protein or fragment thereof is different relative to a concentration value of a reference pancreatic cancer-related protein or fragment thereof from an pancreatic cancer-negative sample; and displaying the result or a pancreatic cancer treatment regime on an electronic display connected directly or wirelessly to the processor for the subject identified as having pancreatic cancer or as having a predisposition of developing pancreatic cancer.

[00139] The displayed result or treatment regime comprises electronic text, optionally with graphical icons. Optionally, the graphical icons are part of an electronic dashboard that displays the result in a format that simplifies the result and/or provides a treatment recommendation based on the result. [00140] As noted, the computer-implemented method may further allow monitoring of pancreatic cancer-related proteins across multiple time points to support a more effective treatment regime. A non-limiting example of such a process is described in Figure 1. The method comprises obtaining a biological sample (e.g., serum sample) at a time point 1 (Tl). The sample is subjected to a proteolysis 10A to produce hydrolyzed proteins, the hydrolyzed proteins are subjected to mass spectrometry 20A and pancreatic cancer-related proteins are measured 30A. The concentrations are compared to a pancreatic cancer negative sample 40A and it is determined whether the concentrations of the protein(s) are increased or decreased relative to the standard 50A. In this non-limiting example, the pancreatic cancer-related proteins are at least one of L-selectin, tetranectin, phospholipid transfer protein and/or fibronectin. In one example of the disclosure, at least one of L-selectin, tetranectin, and/or phospholipid transfer protein are elevated relative to a baseline (e.g., pancreatic negative sample). In this case, the subject is identified as having a possible risk of having pancreatic cancer or developing the disease (YES). If the concentrations of L-selectin, tetranectin, phospholipid transfer protein and/or fibronectin do not differ significantly from the standard, then the subject is identified has having a low pancreatic cancer risk 60 (NO). It is understood that the larger the magnitude of the elevation between the measured pancreatic cancer-related proteins and the pancreatic cancer-related proteins from the pancreatic negative sample, the “worse off’ the individual’s likelihood of having pancreatic cancer or developing the disease. It is desirable that this information is obtained earlier in the individual’s life (e.g., 40 years or below, 35 years or below, 30 years or below, or 25 years or below), so as to increase any benefits from the delay or offset of the progress of the pancreatic cancer.

[00141] In other embodiments, while a smaller magnitude of the elevation between the measured pancreatic cancer-related proteins and the pancreatic cancer-related proteins from the pancreatic negative sample reflects the individual’s low likelihood of having or developing pancreatic cancer up to that point in time, there is no assurance that the magnitude of the elevation will continue to remain small at a later time point. Therefore, it is advisable for these individuals to continually monitor their risk of having or developing pancreatic cancer on a regular basis. For example, if the subject is identified as having a possible risk of having pancreatic cancer or developing the disease (YES), a second biological sample (e.g., serum sample) is obtained at time point 2 (T2), which is after Tl . In some embodiments, the individual’s risk of having or developing pancreatic cancer is measured over the lifetime of the individual (or at least over an extended period of time such as, for example, at least two months, at least four months, at least six months, at least a year, at least two years, at least five years, at least a decade, at least two decades, or at least three decades). The sample is subjected to a proteolysis 10B to produce hydrolyzed proteins, the hydrolyzed proteins are subjected to mass spectrometry 20B and pancreatic cancer-related proteins are measured 3 OB. The concentrations are compared to T2 40B and it is determined whether the protein(s) are increased or decreased relative to T2 concentration levels 50B. If at least one of pancreatic cancer- related proteins selected from L-selectin, tetranectin, phospholipid transfer protein and/or fibronectin are elevated relative to T1 by a threshold value (e.g., at least 10%, at least 20%, at least 30%), then the subject is identified as having a high risk of having pancreatic cancer or developing the disease 70 (YES). The subject is typically identified as having pancreatic cancer after a biopsy is taken and analyzed for the presence of cancerous cells (e.g., using microscopy). If the concentrations of L-selectin, tetranectin, phospholipid transfer protein and/or fibronectin do not differ significantly from Tl, then the subject is identified as having a low pancreatic cancer risk 60 (NO). The pancreatic cancer-related proteins can be measured at a third time point, time point 3 (T3), which is after T2, if required. The concentrations of the pancreatic cancer-related proteins at T3 can be compared to the levels at one or both of T2 and Tl to identify the subject has having a high or low risk of having pancreatic cancer or developing the disease. As a result, the method according to the present disclosure allows for monitoring changes in status of the pancreatic cancer or risk of developing (or redeveloping) pancreatic cancer over time, particularly after any treatment regime. The treatment regime typically involves surgery, but may additionally or alternatively comprise administration of chemotherapeutic agents and/or radiation treatment.

[00142] The following examples describe some exemplary modes of practicing certain methods that are described herein. It should be understood that the examples are for illustrative purposes only and are not meant to limit the scope of the systems and methods described herein.

EXAMPLES

Example 1: Diagnosis and treatment of a patient with stage one pancreatic cancer as determined by monitoring changes in concentrations of pancreatic related proteins over time

[00143] The proteomic profile of a patient was monitored over the course of three years from 2019 to 2022 as part of a multi-omics health assessment provided by the Applicant. Each of the proteins set forth below in Table 1 were identified as exhibiting a significant change in blood concentration (nM) as measured over the three-year period. Surprisingly, certain proteins (L-selectin, tetranectin and phospholipid transfer protein) also showed significant concentration increases at timepoint 2 (T2) relative to timepoint 1 (Tl). On the other hand, fibronectin decreased by 323.98% from timepoint 3 (T3) to timepoint 2 (T2).

Table 1: Changes in concentration of pancreatic cancer-related proteins over time

[00144] L-selectin, Tetranectin and phospholipid transfer protein were elevated at T2 (timepoint 2) and thus were identified as early indicators of pancreatic cancer. The concentrations of each of these proteins were also elevated at T3 (timepoint 3). In addition, fibronectin levels were low at T1 (242.0 nM) and T3 (295.7 nM) timepoints but elevated at T2 (1254.2 nM). A -323.98% change in fibronectin was observed between T2 and T3.

[00145] The results are surprising as Tetranectin levels have been shown to be decreased in pancreatic cancer in previous studies (Caputo et al., 2022, Cancers (Basel), 14(19):4658; and Felix et al., 2013, PloS ONE, 8e82755). However, the inventors found that this protein was increased over the time period of measurement.

[00146] The patient was assessed by a medical practitioner and diagnosed with stage 1 pancreatic cancer. A biopsy was obtained from the patient and examined by microscopy to confirm the diagnosis. The patient underwent surgery to remove the tumour. To the inventors’ knowledge, this is the first positive early stage diagnosis and treatment of pancreatic cancer using the novel proteomic profile identified herein. [00147] The changes in blood concentration of one or a combination of certain pancreatic cancer- related proteins measured over time provides a tool for early-stage detection of pancreatic cancer that has not otherwise been available using known diagnostic approaches. Monitoring of the combination of proteins identified as being elevated in the patient to diagnose and treat pancreatic cancer thus represents a significant advance over the art.

[00148] Other examples of implementations will become apparent in view of the teachings of the present description.

[00149] Note that titles or subtitles may be used throughout the present disclosure for convenience of a reader, but in no way should these limit the scope of the invention. Moreover, certain theories may be proposed and disclosed herein; however, in no way should such theories limit the scope of the invention.

[00150] Elements of the methods and/or systems of the disclosure described in connection with the examples apply mutatis mutandis to other aspects of the disclosure. Therefore, it will be understood that the methods and/or systems of the present disclosure encompasses any methods and/or systems comprising any of the steps and/or components cited herein, in any embodiment wherein each such step or component is independently present as defined herein. Many such methods and/or systems than what is specifically set out herein, can be encompassed.

[00151] The dimensions and values disclosed herein are not to be understood as being strictly limited to the exact numerical values recited. Instead, unless otherwise specified, each such dimension is intended to mean both the recited value and a functionally equivalent range surrounding that value. For example, a dimension disclosed as “40 mm” is intended to mean “about 40 mm”.

[00152] Every document cited herein, including any cross referenced or related patent or application and any patent application or patent to which this application claims priority or benefit thereof, is hereby incorporated herein by reference in its entirety unless expressly excluded or otherwise limited. The citation of any document is not an admission that it is prior art with respect to any disclosure disclosed or claimed herein or that it alone, or in any combination with any other reference or references, teaches, suggests or discloses any such disclosure. Further, to the extent that any meaning or definition of a term in this document conflicts with any meaning or definition of the same term in a document incorporated by reference, the meaning or definition assigned to that term in this document shall govern.

[00153] While particular embodiments of the present disclosure have been illustrated and described, it would be obvious to those skilled in the art that various other changes and modifications can be made without departing from the scope of the present disclosure. It is therefore intended to cover in the appended claims all such changes and modifications that are within the scope of this disclosure.

Claims

1. A method for treating pancreatic cancer in a subj ect, the method comprising:

(i) receiving a proteomic profile from a subject, the proteomic profile previously obtained by:

(a) providing a biological sample obtained from the subject;

(b) measuring concentration levels of one or a combination of, at least two, at least three, at least four or at least five pancreatic cancer-related proteins, or peptide fragment thereof, selected from apolipoprotein Al, apolipoprotein A-II, plasma protease Cl inhibitor, L-sel ectin, tetranectin, phospholipid transfer protein, apolipoprotein M, gelsolin, adipocyte plasma membrane- associated protein, Cis complement factor, C4b complement factor, C6 complement factor and fibronectin from the obtained sample;

(c) comparing the concentration levels of the pancreatic cancer-related proteins, or peptide fragments thereof, from the obtained sample to the concentration levels of reference pancreatic cancer-related proteins or peptide fragments thereof from a pancreatic cancer-negative reference value and/or from a sample obtained at an earlier time point from the subject;

(ii) identifying the subject as being at risk of having pancreatic cancer if the concentration levels of the pancreatic cancer-related proteins, or peptide fragments thereof, from the obtained sample are different relative to the concentration levels of the reference pancreatic cancer-related proteins or peptide fragments thereof, from the pancreatic cancer-negative reference value and/or from a sample obtained at an earlier time point from the subject;

(iii) optionally obtaining a biopsy from the subject so identified as being at risk of having pancreatic cancer in step (ii);

(iv) analyzing the biopsy to determine if cancerous cells are present;

(v) identifying the subject as having pancreatic cancer if the subject is identified as being at risk of having pancreatic cancer based on the proteomic profile in step (ii) and if the cancerous cells are present in the biopsy; and

(vi) optionally removing the cancerous tissue from the subject’s pancreas and/or bile duct(s) if the subject is identified as having pancreatic cancer.

2. A method for diagnosing and treating pancreatic cancer in a subject, the method comprising:

(a) providing a biological sample obtained from the subject; (b) measuring concentration levels of one or a combination of, at least two, at least three, at least four or at least five pancreatic cancer-related proteins, or peptide fragment thereof, selected from apolipoprotein Al, apolipoprotein A-II, plasma protease Cl inhibitor, L-sel ectin, tetranectin, phospholipid transfer protein, apolipoprotein M, gelsolin, adipocyte plasma membrane- associated protein, Cis complement factor, C4b complement factor, C6 complement factor and fibronectin from the obtained sample;

(d) identifying the subject as having pancreatic cancer or at risk of having pancreatic cancer if the concentration levels of the pancreatic cancer-related proteins, or peptide fragments thereof, from the obtained sample are different relative to the concentration levels of the reference pancreatic cancer-related proteins or peptide fragments thereof, from the pancreatic cancernegative reference value and/or from a sample obtained at an earlier time point from the subject; and

(e) optionally treating or causing the treating of the subject so identified as having pancreatic cancer with a pancreatic cancer treatment regime, optionally comprising surgery and/or administration of a chemotherapeutic agent or radiation treatment.

3. A method for diagnosing and treating pancreatic cancer in a subject, the method comprising:

(a) providing a biological sample obtained from the subject;

(b) measuring or having measured in a spectroscopy unit the concentration levels of a combination of pancreatic cancer-related proteins, or peptide fragments thereof, selected from selected from apolipoprotein Al; apolipoprotein A-II, plasma protease Cl inhibitor, L-selectin, tetranectin, phospholipid transfer protein, apolipoprotein M, gelsolin, adipocyte plasma membrane-associated protein, Cis complement factor, C4b complement factor, C6 complement factor and fibronectin from the obtained sample;

(c) comparing or having compared concentration levels of the pancreatic cancer-related proteins, or peptide fragments thereof, as determined in the spectroscopy unit to the concentration levels of reference pancreatic cancer- related proteins, or peptide fragments thereof, from a pancreatic cancer-negative reference value and/or from a sample obtained at an earlier time point from the subject;

(d) identifying the subject as having pancreatic cancer or at risk of having pancreatic cancer if the concentration levels of the pancreatic cancer-related proteins, or peptide fragments thereof, from the obtained sample are different relative to the concentration levels of the reference pancreatic cancer-related proteins, or peptide fragments thereof, from the pancreatic cancernegative sample and/or from a sample obtained at an earlier time point from the subject; and

4. The method according to claim 1, 2 or 3, wherein the pancreatic cancer treatment comprises lowering the blood levels of one or more of the pancreatic cancer-related proteins or peptide fragments thereof in the subject diagnosed as having the pancreatic cancer.

5. The method according to claim 4, wherein the adjustment of the blood levels of one or more of the pancreatic cancer-related proteins or peptide fragments thereof in the subject occurs until the pancreatic cancer-related proteins or peptide fragments thereof are lowered to a predetermined level in the subject.

6. The method according to any one of claims 1 to 5, wherein the identifying step occurs upon determination that the concentration levels of at least one, at least two, at least three, at least four or at least five of the pancreatic cancer-related proteins or peptide fragments thereof from the obtained sample are elevated by about 10% or more, 20% or more, about 30% or more, about 40% or more, about 50% or more, about 60% or more, or about 70% or more relative to the concentration levels of the reference pancreatic cancer-related proteins or peptide fragments thereof from the pancreatic cancer-negative reference value and/or relative to concentrations levels in a sample obtained previously from the subject.

7. The method according to any one of claims 1 to 6, wherein measuring the concentration levels of the pancreatic cancer-related proteins or peptide fragments comprises measuring at least one, at least two, least three, or each one of L-selectin, tetranectin, phospholipid transfer protein and fibronectin.

8. The method according to any one of claims 1 to 7, wherein the concentration level of at least tetranectin is measured.

9. The method according to any one of claims 1 to 8, wherein the obtained sample is blood or urine.

10. The method according to any one of claims 1 to 8, wherein the obtained sample is serum or plasma.

11. The method according to claim 9, wherein the obtained sample is urine.

12. The method according to any one of claims 1 to 8, wherein the pancreatic cancer-related proteins or peptide fragments thereof are measured by a spectroscopic technique, wherein the spectroscopic technique is selected from the group consisting of liquid chromatography, gas chromatography, liquid chromatography mass spectrometry, gas chromatography mass spectrometry, high performance liquid chromatography mass spectrometry, capillary electrophoresis mass spectrometry, nuclear magnetic resonance spectrometry (NMR), raman spectroscopy and infrared spectroscopy.

13. The method according to claim 12, wherein the spectroscopic technique comprises mass spectrometry.

14. The method according to any one of claims 1 to 8, wherein the comparison of the concentration levels of the pancreatic cancer-related proteins or peptide fragments thereof or peptide fragments thereof from the obtained sample to the concentration levels of the reference values comprises using multivariate statistical analysis.

15. The method according to claim 14, wherein the multivariate statistical analysis is selected from principal component analysis (PC A), or partial least squares projects to latent structures discriminant analysis (PLS-DA).

16. A method of monitoring protein or peptide fragments in a subject and treating pancreatic cancer in a subject, the method comprising:

(a) providing a first biological sample obtained from the subject at a first time point;

(b) assessing a first pancreatic cancer-related proteomic profile by measuring concentration levels of at least one, at least two, at least three, at least four or at least five pancreatic cancer- related proteins, or peptide fragments thereof, selected from pancreatic cancer-related proteins or peptide fragments thereof selected from apolipoprotein Al; apolipoprotein A-II, plasma protease Cl inhibitor, L-selectin, tetranectin, phospholipid transfer protein, apolipoprotein M, gelsolin, adipocyte plasma membrane-associated protein, Cis complement factor, C4b complement factor, C6 complement factor and fibronectin from the first biological sample;

(c) comparing the first pancreatic cancer-related proteomic profile with a reference pancreatic cancer-related proteomic profile from a pancreatic cancer-negative sample;

(d) determining that there is a first difference between the first pancreatic cancer-related proteomic profile and the reference pancreatic cancer-related proteomic profile from the pancreatic cancer-negative sample, the first difference being indicative of pancreatic cancer;

(e) providing a second biological sample obtained from the subject at a second time point that is after the first time point;

(f) assessing a second pancreatic cancer-related proteomic profile by measuring concentration levels of the pancreatic cancer-related proteins or peptide fragments thereof from the second biological sample;

(g) comparing the second pancreatic cancer-related proteomic profile with the reference pancreatic cancer-related proteomic profile from the pancreatic cancer-negative sample;

(h) determining that there is a second difference between the first pancreatic cancer-related proteomic profile and the reference pancreatic cancer-related proteomic profile from the pancreatic cancer-negative sample, the second difference being indicative of pancreatic cancer;

(i) determining pancreatic cancer progression or a risk of having pancreatic cancer based at least in part on the first and second differences; and (j) optionally treating or causing the treating of the subject if identified as having pancreatic cancer with a pancreatic cancer treatment regime, optionally comprising surgery and/or administration of an anti-cancer therapeutic agent or radiation treatment.

17. The method according to claim 16, wherein the period of time between the first time and the second time points is at least 1 month, at least 2 months, at least 3 months or at least 6 months.

18. The method according to claim 16 or 17, wherein measuring the concentration levels of the pancreatic cancer-related proteins or peptide fragments thereof from the first and/or second biological samples comprises measuring at least one, at least two, least three, or each one of L- selectin, tetranectin, phospholipid transfer protein and fibronectin.

19. The method of claim 16, 17 or 18, wherein the concentration level of at least tetranectin is measured.

20. The method according to claim 17, wherein the first sample, the second sample, or both are blood or urine or wherein both samples are the same specimen type and are selected from serum, plasma or urine.

21. A kit for diagnosis of pancreatic cancer comprising:

(a) a detector configured to detect concentration levels of at least one, at least two, at least three, at least four or at least five pancreatic cancer-related proteins, or peptide fragments thereof, selected from apolipoprotein Al; apolipoprotein A-II, plasma protease Cl inhibitor, L-selectin, tetranectin, phospholipid transfer protein, apolipoprotein M, gelsolin, adipocyte plasma membrane-associated protein, Cis complement factor, C4b complement factor, C6 complement factor and fibronectin obtained from a biological sample;

(b) a composition comprising apolipoprotein Al; apolipoprotein A-II, plasma protease Cl inhibitor, L-selectin, tetranectin, phospholipid transfer protein, apolipoprotein M, gelsolin, adipocyte plasma membrane-associated protein, Cis complement factor, C4b complement factor, C6 complement factor and fibronectin in control levels corresponding to a control group of pancreatic cancer-negative subjects;

(c) a multivariate analysis system configured to analyze a difference in the concentration levels of the pancreatic cancer-related proteins or peptide fragments thereof and the control levels, and

(d) optionally, providing instructions for a pancreatic cancer diagnosis method, wherein the method comprises measuring, using the detector, the levels of the pancreatic cancer-related proteins or peptide fragments thereof from the obtained biological sample, and comparing the levels of the obtained pancreatic cancer-related proteins or peptide fragments thereof to the control levels of the pancreatic cancer-related proteins or peptide fragments thereof obtained from pancreatic cancer-negative subjects and/or from a sample obtained at an earlier time point from the subject.

22. The kit according to claim 21, wherein the detector comprises a multi -proteomic detector configured to measure the levels of the pancreatic cancer-related proteins, or peptide fragments thereof, comprising the apolipoprotein Al, apolipoprotein A-II, plasma protease Cl inhibitor, L- selectin, tetranectin, phospholipid transfer protein, apolipoprotein M, gelsolin, adipocyte plasma membrane-associated protein, Cis complement factor, C4b complement factor, C6 complement factor and fibronectin.

23. The kit according to claim 21 or 22, wherein detector is configured to measure the concentration levels of the pancreatic cancer-related proteins or peptide fragments comprising at least one, at least two, least three, or each one of L-selectin, tetranectin, phospholipid transfer protein and fibronectin.

24. The kit of claim 23, wherein the detector is configured to measure at least tetranectin.

25. A computer-implemented method for processing a biological sample of a subject, diagnosing pancreatic cancer and treating the pancreatic cancer, the computer-implemented method comprising:

(a) receiving a biological sample obtained from the subject; (b) processing the sample in a spectroscopy unit directly or wirelessly linked to a processing device, the processing device having memory for storing measurement data from the spectroscopy unit;

(c) in the spectroscopy unit, measuring levels of least one, at least two, at least three, at least four or at least five pancreatic cancer-related proteins, or peptide fragments thereof, selected from apolipoprotein Al, apolipoprotein A-II, plasma protease Cl inhibitor, L-sel ectin, tetranectin, phospholipid transfer protein, apolipoprotein M, gelsolin, adipocyte plasma membrane- associated protein, Cis complement factor, C4b complement factor or C6 complement factor and fibronectin and storing the measurement data in the processor;

(d) comparing the stored measurement data to a reference value in the memory representing a pancreatic cancer- negative sample, optionally using multivariate statistical analysis;

(e) storing on the processing device a result corresponding to at least one, at least two, at least three, at least four or at least five pancreatic cancer-related proteins or peptide fragments thereof selected from the group consisting of apolipoprotein Al, apolipoprotein A-II, plasma protease Cl inhibitor, L-selectin, tetranectin, phospholipid transfer protein, apolipoprotein M, gelsolin, adipocyte plasma membrane-associated protein, Cis complement factor, C4b complement factor or C6 complement factor and fibronectin from the obtained sample, wherein the result identifies the subject as having pancreatic cancer or a risk of having pancreatic cancer if the measurement data representing the levels of the pancreatic cancer-related proteins or peptide fragments thereof are different relative to a concentration levels of reference pancreatic cancer-related proteins, or peptide fragments thereof, from a pancreatic cancer-negative sample;

(f) displaying the result on an electronic display connected directly or wirelessly to the processor for the subject identified as having pancreatic cancer, a risk of having pancreatic cancer or as having a predisposition of developing pancreatic cancer; and

(g) optionally treating or causing treatment of the subject identified as having pancreatic cancer with a pancreatic cancer regime, optionally comprising surgery and/or administration of an anticancer therapeutic agent or radiation treatment.

26. The method of claim 25, wherein the displayed result is included in a user interface that is a dashboard.

27. The method of claim 25 or 26, wherein the displayed result is part of multi-omic information displayed on the user interface.

28. The method according to claim 25, 26 or 27, wherein the spectroscopy unit comprises a detector or is operatively connected to a detector that is configured to measure the concentration levels of the pancreatic cancer-related proteins or peptide fragments optionally configured to measure at least one, at least two, least three, or each one of L-selectin, tetranectin, phospholipid transfer protein and fibronectin.

29. The method of claim 28, wherein the detector is configured to measure at least tetranectin.

30. A method for diagnosing and treating pancreatic cancer in a subject, the method comprising:

(a) providing a biological sample obtained from the subject;

(b) measuring concentration levels of at least one, at least two, at least three, at least four or at least five pancreatic cancer-related proteins or peptide fragments thereof selected from apolipoprotein Al, apolipoprotein A-II, plasma protease Cl inhibitor, L-selectin, tetranectin, phospholipid transfer protein, apolipoprotein M, gelsolin, adipocyte plasma membrane- associated protein, Cis complement factor, C4b complement factor or C6 complement factor and fibronectin;

(c) comparing the concentration levels of the pancreatic cancer-related proteins or peptide fragments thereof from the obtained sample to the concentration levels of reference pancreatic cancer-related proteins or peptide fragments thereof from a pancreatic cancer- negative sample and/or from a sample obtained at an earlier time point from the subject;

(d) identifying the subject as having pancreatic cancer or a risk of having pancreatic cancer if the concentration levels of the pancreatic cancer-related proteins or peptide fragments thereof from the obtained sample are different relative to the concentration levels of the reference pancreatic cancer-related proteins or peptide fragments thereof from the pancreatic cancer-negative sample and/or from a sample obtained at an earlier time point from the subject; and

(e) optionally treating or causing the treating of the subject so identified with a pancreatic cancer treatment regime or radiation treatment.

31. The method according to claim 30, wherein measuring the concentration levels of the pancreatic cancer-related proteins or peptide fragments thereof from the first and/or second biological samples comprises measuring at least one, at least two, least three, or each one of L- selectin, tetranectin, phospholipid transfer protein and fibronectin.

32. The method of claim 30 or 31, wherein the concentration level of at least tetranectin is measured.

33. A method for diagnosing and treating pancreatic cancer in a subject, the method comprising:

(a) providing a first biological sample obtained from the subject;

(b) at a first time point, measuring concentration levels of at least one, at least two, at least three, at least four or at least five pancreatic cancer-related proteins or peptide fragments thereof selected from apolipoprotein Al, apolipoprotein A-II, plasma protease Cl inhibitor, L-selectin, tetranectin, phospholipid transfer protein, apolipoprotein M, gelsolin, adipocyte plasma membrane-associated protein, Cis complement factor, C4b complement factor or C6 complement factor and fibronectin from the obtained sample;

(d) at a second time point, measuring concentration levels of at least one, at least two, at least three, at least four or at least five pancreatic cancer-related proteins or peptide fragments thereof selected from apolipoprotein Al; apolipoprotein A-II, plasma protease Cl inhibitor, L-selectin, tetranectin, phospholipid transfer protein, apolipoprotein M, gelsolin, adipocyte plasma membrane-associated protein, Cis complement factor, C4b complement factor or C6 complement factor and fibronectin in a second biological sample obtained from the subject;

(e) comparing the concentration levels at the second time point of the pancreatic cancer-related proteins or peptide fragments thereof from the obtained sample to the concentration levels of reference pancreatic cancer-related proteins or peptide fragments thereof from a pancreatic cancer- negative sample and/or from a sample obtained at the first time point or the earlier time point from the subject;

(f) identifying the subject as having pancreatic cancer or a risk of having pancreatic cancer if the concentration levels of the pancreatic cancer-related proteins or peptide fragments thereof from the first and second obtained samples are different relative to the concentration levels of the reference pancreatic cancer-related proteins or peptide fragments thereof from the pancreatic cancer-negative sample, and/or relative to a sample obtained at the first time point; and

(g) optionally treating or causing the treating of the subject if so identified as having pancreatic cancer with a pancreatic cancer treatment regime.

34. The method according to claim 33, wherein the identifying step (f) occurs upon determination that the concentration levels of at least one, at least two, at least three, at least four, or at least five of the pancreatic cancer-related proteins or peptide fragments thereof from the obtained sample are elevated by about 10% or more, about 20% or more, about 30% or more, about 40% or more, about 50% or more, about 60% or more, or about 70% or more relative to the concentration levels of the reference pancreatic cancer-related proteins or peptide fragments thereof from the pancreatic cancer-negative sample.

35. The method according to claim 33, wherein the identifying step (f) occurs upon determination that the concentration levels of at least three, at least four, or at least five of the pancreatic cancer-related proteins or peptide fragments thereof from the obtained sample are elevated by about 10% or more, about 20% or more, about 30% or more, about 40% or more, about 50% or more, about 60% or more or about 70% or more relative to the concentration levels of the reference pancreatic cancer-related proteins or peptide fragments thereof from the pancreatic cancer-negative sample.

36. The method according to claim 33, wherein measuring the concentration levels of the pancreatic cancer-related proteins or peptide fragments thereof from the first and/or second biological samples comprises measuring at least one, at least two, least three, or each one of L- selectin, tetranectin, phospholipid transfer protein and fibronectin.

37. The method of any one of claims 33 to 36, wherein the concentration level of at least tetranectin is measured.

38. The method according to any one of claims 33 to 37, wherein the obtained sample is blood or urine, or is serum, plasma or urine.

39. The method according to any one of claims 33 to 38, wherein the pancreatic cancer- related proteins or peptide fragments thereof are measured by a spectroscopic technique, wherein the spectroscopic technique is selected from the group consisting of liquid chromatography, gas chromatography, liquid chromatography mass spectrometry, gas chromatography mass spectrometry, high performance liquid chromatography mass spectrometry, capillary electrophoresis mass spectrometry, nuclear magnetic resonance spectrometry (NMR), raman spectroscopy, and infrared spectroscopy.

40. The method according to any one of claims 33 to 39, wherein the comparison of the concentration levels of the pancreatic cancer-related proteins or peptide fragments thereof from the obtained sample to the concentration levels of the reference pancreatic cancer-related proteins or peptide fragments thereof from the pancreatic cancer-negative sample comprises multivariate statistical analysis.

41. The method according to any one of claims 33 to 40, wherein measuring the concentration levels of the pancreatic cancer-related proteins or peptide fragments thereof from the second biological sample comprises measuring at least one, at least two, least three, or each one of L-selectin, tetranectin and phospholipid transfer protein and wherein if the measured levels of L-selectin, tetranectin and/or phospholipid transfer protein in the second biological sample, when compared to respective concentration levels measured at the first time point, are elevated by at least 10%, 15%, 20% or 25%, the subject is identified as having pancreatic cancer or as having a risk of having pancreatic cancer.

42. The method according to any one of claims 33 to 41, wherein the concentration level of at least fibronectin is measured and wherein if the measured level of fibronectin in the second biological sample, when compared to a respective concentration level measured at the first time point, is elevated or decreased by at least 10%, 15%, 20% or 25%, the subject is identified as having pancreatic cancer or as having a risk of having pancreatic cancer.

43. A proteolyzed sample for use in mass spectrometry to diagnose pancreatic cancer in a subject comprising one or a combination of peptide fragments of apolipoprotein Al, apolipoprotein A-II, plasma protease Cl inhibitor, L-selectin, tetranectin, phospholipid transfer protein, apolipoprotein M, gelsolin, adipocyte plasma membrane-associated protein, Cis complement factor, C4b complement factor, C6 complement factor and fibronectin.

44. A proteolyzed sample for use in mass spectrometry to diagnose pancreatic cancer in a subject comprising a peptide fragment of L-selectin, tetranectin, phospholipid transfer protein and/or fibronectin.

45. The method of any one of the preceding claims, further comprising obtaining a biopsy sample from the subject identified as having a risk of having pancreatic cancer after measurement of the pancreatic cancer proteins or fragments thereof and if cancerous cells are identified in the sample, surgically removing cancerous tissue from the pancreas and/or bile duct(s) of the subject.

46. The method or kit of any one claims 1 to 45, wherein levels of the Tetranectin increase over time as measured at two or more time points within in a 1 -month to 3 -year time period or are elevated at a single time point over a control.

47. The method or kit of any one of claims 1 to 45, further comprising measuring levels of at least one of L-selectin and phospholipid transfer protein, and wherein the levels of at least one of L-selectin and phospholipid transfer protein increase over time as measured at two or more time points within in a 1 -month to 3 -year time period or are elevated at a single time point over a control.

48. The method of claim 46, further comprising measuring levels of at least one of L-selectin and phospholipid transfer protein, and wherein the levels of at least one of L-selectin and phospholipid transfer protein increase over time as measured at two or more time points within in a 1-month to 3-year time period or are elevated at a single time point over a control.

49. The method or kit of claim 46, 47 or 48, further comprising measuring levels of L- selectin and phospholipid transfer protein, and wherein the levels of L-selectin and phospholipid transfer protein increase over time as measured at two or more time points within in a 1-month to 3-year time period or are elevated at a single time point over a control.

50. The method or kit of any one of claims 46 to 49, further comprising measuring fibronectin.

51. The method or kit of any one of claims 46 to 50, further comprising measuring at least one of apolipoprotein Al, apolipoprotein A-II, plasma protease Cl inhibitor, apolipoprotein M, gelsolin, adipocyte plasma membrane-associated protein, Cis complement factor, C4b complement factor, C6 complement factor or a combination thereof.