[go: up one dir, main page]

WO2013048174A2 - Kit pour le diagnostic de l'adénocarcinome pancréatique, comprenant des moyens de mesure du ca19-9, de la cathepsine d et la métalloprotéinase matricielle-7 - Google Patents

Kit pour le diagnostic de l'adénocarcinome pancréatique, comprenant des moyens de mesure du ca19-9, de la cathepsine d et la métalloprotéinase matricielle-7 Download PDF

Info

Publication number
WO2013048174A2
WO2013048174A2 PCT/KR2012/007895 KR2012007895W WO2013048174A2 WO 2013048174 A2 WO2013048174 A2 WO 2013048174A2 KR 2012007895 W KR2012007895 W KR 2012007895W WO 2013048174 A2 WO2013048174 A2 WO 2013048174A2
Authority
WO
WIPO (PCT)
Prior art keywords
cathepsin
mmp
pancreatic cancer
kit
measuring
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/KR2012/007895
Other languages
English (en)
Korean (ko)
Other versions
WO2013048174A3 (fr
Inventor
이수연
김종원
박형두
이종균
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Samsung Life Public Welfare Foundation
Original Assignee
Samsung Life Public Welfare Foundation
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Samsung Life Public Welfare Foundation filed Critical Samsung Life Public Welfare Foundation
Publication of WO2013048174A2 publication Critical patent/WO2013048174A2/fr
Publication of WO2013048174A3 publication Critical patent/WO2013048174A3/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Images

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G01N33/57407—Specifically defined cancers
    • G01N33/57438—Specifically defined cancers of liver, pancreas or kidney
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/531—Production of immunochemical test materials
    • G01N33/532—Production of labelled immunochemicals
    • G01N33/533—Production of labelled immunochemicals with fluorescent label
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/531—Production of immunochemical test materials
    • G01N33/532—Production of labelled immunochemicals
    • G01N33/534—Production of labelled immunochemicals with radioactive label
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids

Definitions

  • the present invention relates to a pancreatic cancer diagnostic kit comprising the measuring means of CA19-9, cathepsin D and matrix metalloproteinase-7, and more specifically, the present invention is a marker for diagnosing pancreatic cancer, CA19-9, cathepsin D and MMP
  • the present invention relates to a pancreatic cancer diagnostic composition comprising an agent for measuring mRNA or protein levels of a gene encoding -7, a pancreatic cancer diagnostic kit including the pancreatic cancer diagnostic composition, and a pancreatic cancer diagnostic method using the composition or the kit.
  • Pancreatic adenocarcinoma is the 14th most common cancer in the world and has a poor prognosis with less than 5% 5 year survival and a very poor prognosis that kills more than half of the patients diagnosed within 6 months. It is known as a disease that indicates. About 95% of these pancreatic tumors are PDACs (ductal adenocarcinomas) and the remaining 5% are known as Langerhan's islet cell tumors. PDACs are very aggressive malignancies with very low mean survival rates and have very low diagnostic success rates. It is known to exhibit high resistance to chemotherapeutic agents.
  • pancreatic cancer is known to have an acquired pathogen as a direct pathogen.
  • Pancreatic Intraepithelial Neoplsia Pancreatic Intraepithelial Neoplsia
  • the present inventors have diligently researched to develop a method for more efficiently diagnosing pancreatic cancer.
  • the combination of CA19-9, cathepsin D and MMP-7 is used as a biomarker, the sensitivity and specificity of pancreatic cancer is remarkably increased. It was confirmed that it can increase, and the present invention was completed.
  • pancreatic cancer diagnostic composition comprising an agent for measuring mRNA or protein levels derived from polynucleotides encoding CA19-9, cathepsin D and MMP-7.
  • Another object of the present invention is to provide a pancreatic cancer diagnostic kit comprising the pancreatic cancer diagnostic composition.
  • Still another object of the present invention is to provide a method for diagnosing pancreatic cancer using the composition or kit.
  • pancreatic cancer diagnostic kit of the present invention since the onset of pancreatic cancer can be diagnosed early, it can be widely used for the treatment of pancreatic cancer more effectively.
  • 1 is a box whisker plot of serum levels of cathepsin D and MMP-7 in a training set comprising a healthy subject (H), a patient with chronic pancreatitis (CP) and a patient with pancreatic adenocarcinoma (PDAC).
  • H healthy subject
  • CP chronic pancreatitis
  • PDAC pancreatic adenocarcinoma
  • ROC receiver manipulation characteristic
  • FIG. 3 is a box whisker plot of serum levels of cathepsin D and MMP-7 in healthy subjects (H), patients with chronic pancreatitis (CP) and patients with stage I or II pancreatic adenocarcinoma (PDAC).
  • H healthy subjects
  • CP chronic pancreatitis
  • PDAC pancreatic adenocarcinoma
  • FIG. 4 shows serum levels of cathepsin D, MMP-7 and CA19-9 in patients and control groups with PDAC at various stages.
  • the invention comprises an agent for measuring mRNA or protein levels derived from polynucleotides encoding carbohydrate antigen 19-9 (CA19-9), cathepsin D and matrix metalloproteinase-7 (MMP-7).
  • CA19-9 carbohydrate antigen 19-9
  • MMP-7 matrix metalloproteinase-7
  • CA19-9 carbohydrate antigen 19-9 of the present invention refers to glycolipids in which Lewis blood type antigens are modified.
  • CA19-9 increases the patient's blood concentration at the onset of colorectal cancer, gastric cancer, and pancreatic cancer but lacks tissue specificity, it does not increase in blood types that do not express Lewis antigen, and thus cannot be used for screening or diagnosis. There is this.
  • the inventors simultaneously measured mRNA or protein levels derived from polynucleotides encoding cathepsin D and MMP-7 with CA19-9.
  • pancreatic cancer diagnostic marker From the polynucleotides encoding CA19-9, cathepsin D and MMP-7, Derived mRNA or protein served as pancreatic cancer diagnostic marker.
  • the amino acid sequence of the CA19-9 or the polynucleotide sequence encoding the same may be obtained from a known database including NCBI, and may be, for example, NCBI Reference Sequence: NP_004354.2, but may be used as a pancreatic cancer marker. It is not particularly limited as long as it has an activity of -9.
  • cathepsin D refers to an endopeptidase which is present in intracellular lysosomes, has a molecular weight of 30 to 40 kDa, and hydrolyzes denatured hemoglobin at pH 3-4.
  • the amino acid sequence of the cathepsin D or the polynucleotide sequence encoding the same may be obtained from a known database including NCBI, and may be GenBank: CAB57223.1, for example, but may be used as a pancreatic cancer marker. It does not specifically limit as long as it has the activity of.
  • matrix metalloproteinase-7 refers to proteolytic enzymes involved in the degradation of extracellular matrix, also called matrilysin.
  • the MMP-7 is secreted in the form of precursor proteins that are cleaved by extracellular proteases and is involved in the healing of wounds as well as the degradation of proteoglycans, fibronectin, elastin, casein and the like.
  • MMP-7 is used as a biomarker for bladder cancer, gastric cancer, and colorectal cancer.
  • the amino acid sequence of the MMP-7 or the polynucleotide sequence encoding the same may be obtained from a known database including NCBI, and may be, for example, UniProtKB / Swiss-Prot: P50280.1, but may be used as a pancreatic cancer marker. It is not particularly limited so long as it has the activity of MMP-7.
  • pancreatic cancer diagnostic markers are a substance capable of diagnosing pancreatic cancer cells by distinguishing them from normal cells, polypeptides showing an increased pattern in pancreatic cancer cells compared to normal cells or Organic biomolecules such as nucleic acids (eg mRNA), lipids, glycolipids, glycoproteins, sugars (monosaccharides, disaccharides, oligosaccharides, etc.) and the like.
  • nucleic acids eg mRNA
  • lipids lipids
  • glycolipids glycoproteins
  • sugars monosaccharides, disaccharides, oligosaccharides, etc.
  • pancreatic cancer diagnostic markers may be mRNAs or proteins derived from polynucleotides encoding CA19-9, cathepsin D and MMP-7.
  • mRNA level measurement refers to a process of confirming the presence and expression level of mRNA derived from a polynucleotide encoding pancreatic cancer markers in a biological sample to diagnose pancreatic cancer, and preferably The process of measuring quantity.
  • RTPCR reverse transcriptase
  • RT competitive reverse transcriptase
  • RPA RNase protection assay
  • the term "measurement of protein levels” refers to a process of confirming the presence and degree of expression of a protein derived from a polynucleotide encoding pancreatic cancer markers in a biological sample to diagnose pancreatic cancer. The process of measuring quantity.
  • Western blot ELISA (enzyme linked immunosorbent assay, ELISA), radioimmunoassay (RIA), radioimmunodiffusion, radioimmunodiffusion, Ouchterlony immunodiffusion, rocket ( rocket immunoelectrophoresis, tissue immunostaining, immunoprecipitation assay, complement fixation assay, fluorescence activated cell sorter (FACS), protein chip, etc.
  • the present invention is not particularly limited so long as it is used in a method capable of measuring the amount of a protein derived from a polynucleotide encoding a pancreatic cancer marker.
  • agent to measure means means for measuring the level of the mRNA or protein of the CA19-9, cathepsin D and MMP-7, preferably a primer, mRNA that can amplify the mRNA It may be a probe that can be detected, an antibody or an aptamer that can bind to the protein, etc., but as long as it shows an effect of measuring the level of mRNA or protein of the CA19-9, cathepsin D and MMP-7. It is not specifically limited to this.
  • the term "primer" of the present invention refers to a gene fragment capable of complementarily binding to a terminal region of a desired gene region, a variant of the gene fragment, etc., in order to amplify a region of a desired gene through PCR. Consists of 15 to 30 nucleotides.
  • the primer need not be completely complementary to the gene region of interest, but should be sufficiently complementary to hybridize with the region. If the primer is used, it can be used for determining the base sequence of the gene region of interest, cloning the gene region of interest. In the present invention, the primer can be used to confirm the expression level of mRNA derived from the polynucleotide encoding the pancreatic cancer marker.
  • probe refers to a gene fragment consisting of a base sequence capable of complementarily binding to a target site of a gene of interest and a labeling material bound to the base sequence, a variant of the gene fragment, and the like. Probes can be used to directly determine whether the target site is present in the sample. In the present invention, the probe may be used to quantify mRNA derived from a polynucleotide encoding a pancreatic cancer marker.
  • the primer or probe may be chemically synthesized using phosphoramidite solid support methods, or other well known methods. Such nucleic acid sequences can also be modified using many means known in the art. These variations
  • an antibody refers to a specific protein molecule directed against an antigenic site.
  • an antibody refers to an antibody that specifically binds to pancreatic cancer marker proteins and includes all polyclonal antibodies, monoclonal antibodies, recombinant antibodies or functional fragments thereof.
  • the functional fragment means at least a fragment having an antigen binding function, and may be Fab, F (ab '), F (ab') 2, Fv, or the like.
  • polyclonal antibodies can be produced by methods well known in the art for injecting the colon cancer marker protein antigens described above into an animal and collecting blood from the animal to obtain serum comprising the antibody.
  • polyclonal antibodies can be prepared from any animal species host such as goat, rabbit, sheep, monkey, horse, pig, bovine dog.
  • Monoclonal antibodies can also be prepared using hybridoma methods, or phage antibody library techniques, which are well known in the art.
  • Antibodies prepared by the above method can be isolated and purified using methods such as gel electrophoresis, dialysis, salt precipitation, ion exchange chromatography, affinity chromatography, and the like.
  • diagnosis of the present invention means all actions to confirm the presence or characteristic of a pathological condition.
  • diagnosis is considered to be any act of confirming the development of pancreatic cancer.
  • the specificity was fixed at 80% to compare the sensitivity of individual biomarkers with different combinations in the training set, the proportion of patients with elevated blood levels above the cut-off level was determined by CA19-9, an established tumor marker. Cathepsin Dsms was less than 54% at 74%, but MMP-7 was 72% at a similar level.
  • the AUC of CA19-9 was 0.84 and the combination of CA19-9, MMP-9 and TIMP-1 did not improve diagnostic accuracy for PDAC detection (42). Since the purpose of the present invention is to demonstrate the performance of new biomarkers as screening tools, we investigated which combination of biomarkers exhibited better sensitivity.
  • the combination of cathepsin D and CA19-9 showed excellent sensitivity and AUC compared to the CA19-9 single marker, with sensitivity increased from 74% to 86% and AUC from 0.835 to 0.875 after cathepsin D combination. .
  • sensitivity and AUC increased from 74% to 85% and AUC increased from 0.835 to 0.900, respectively, compared to using CA19-9 alone. These values showed the best results with sensitivity (88%) and AUC (0.849) when three biomarkers (CA19-9, cathepsin D and MMP-7) were combined.
  • the inventors have determined that the measurement of CA19-9 and MMP-7 in serum is the best screening tool for the diagnosis of patients with PC. Although the expression levels of cathepsin D and MMP-7 differed between PDAC and control subjects, there were no differences between PDAC stages.
  • cathepsin D and MMP-7 are expressed and secreted during the early stages of PDAC (I and II). Thus, cathepsin D and MMP-7 can be used for initial detection and screening of PDAC. In contrast, CA19-9 expression generally increases at later stages.
  • the cutoffs from the training set were validated using 285 separate evaluation sets, and the sensitivity (89%) and AUC (0.910) were combined with three biomarkers (CA19-9, cathepsin D and MMP-7).
  • the diagnostic sensitivity was higher than that of CA19-9 alone (78%) and AUC (0.0.881).
  • the present invention provides a pancreatic cancer diagnostic kit comprising the pancreatic cancer diagnostic composition and a means for detecting the composition.
  • the kit may include in the form of a biochip, such as a protein chip, a DNA chip, and the like, each of the formulations contained in the composition on a glass substrate for convenience of use, and means for detecting the composition.
  • a secondary probe that can bind to the primer or probe included in the composition and complementary to the label or the secondary probe in the form of bound label, or the secondary antibody to which the label is bound to the antibody or aptamer included in the composition.
  • the labeling substance may be a chromophore, a fluorescent substance, a radioisotope, or the like.
  • the pancreatic cancer diagnostic kit may be a kit for performing reverse transcriptase analysis, DNA chip analysis, or ELISA.
  • a diagnostic kit comprising essential elements necessary for performing a reverse transcriptase reaction assay may include respective primer pairs specific for a marker gene and primers specific for the nucleic acid sequence of the control gene. It may further include. Indeed, the reverse transcriptase kits can be used in test tubes or other suitable containers, reaction buffers (pH and magnesium concentrations vary), enzymes such as deoxynucleotides (dNTPs), Taq-polymerases and reverse transcriptases, DNAse, RNAse inhibitors. It may be implemented in a form including DEPC-water, sterile water and the like.
  • a diagnostic kit comprising essential elements necessary for performing a DNA chip analysis method is to prepare a substrate on which a cDNA or oligonucleotide corresponding to a gene or fragment thereof is attached, and a fluorescence-labeled probe.
  • Reagents, agents, enzymes, and the like may be included, and the substrate may include cDNA or oligonucleotide corresponding to a control gene or fragment thereof.
  • Antibodies with little cross-reactivity can be monoclonal antibodies, polyclonal antibodies or recombinant antibodies.
  • the ELISA kit may comprise an antibody specific for the control protein.
  • Other ELISA kits can bind reagents that can detect bound antibodies, such as labeled secondary antibodies, chromophores, enzymes (eg conjugated with the antibody) and substrates or antibodies thereof. Other materials and the like.
  • the present invention provides a pancreatic cancer diagnostic method using the pancreatic cancer diagnostic kit.
  • the method for diagnosing pancreatic cancer of the present invention comprises the steps of: (i) measuring protein expression levels of CA19-9, cathepsin D and MMP-7 from isolated biological samples of normal individuals and isolated biological samples of individuals to be detected; And, (ii) detecting protein expression levels of CA19-9, cathepsin D and MMP-7 measured from isolated biological samples of normal individuals, compared to those measured from isolated biological samples of the subjects to be detected.
  • the sample is not particularly limited, but may be blood or serum.
  • each serum from the blood of the normal person or the subject to be detected is Each serum obtained above was reacted by adding an antibody or aptamer capable of specifically binding to CA19-9, cathepsin D or MMP-7 to a protein chip immobilized on a glass substrate, and then labeled secondary antibody. Adding a reaction and measuring the signal generated from the label bound to the protein chip; And (iii) analyzing the signal generated from the label bound to the protein chip to measure the blood levels of CA19-9, cathepsin D and MMP-7, thereby diagnosing pancreatic cancer.
  • the training set includes 70 controls including 109 PDAC patients and 40 normal and 30 CP patients, and the evaluation set includes 139 PDAC patients and 74 normal and 72 CP patients. 146 controls were included.
  • PDAC patients were divided into four groups: two patients with stage I, 59 patients with stage II, 47 patients with stage III, and 140 patients with stage IV. At this time, the normal persons were recruited from those who visited the health promotion center and showed no clinical or biochemical evidence of any disease.
  • PDACs were graded according to the TNM classification of malignant tumors: stage I: tumors restricted to gland; Phase II: Progression of regional expansion, no nodule involvement; Stage III: Involvement of nasal lymph nodes; Step VI: Long Range Transition.
  • the inventors used cathepsin D (Millipore, Billerica, Calif.) From the serum of each subject prepared in Example 1-1 using a Bioplex luminex analyzer (Bio-Rad Laboratories, Hercules, CA, USA) and a multiplex kit (fluorokine MAP). Serum of biomarkers including Massachusetts, USA), TIMPs (-1, -3 and -4; R & D Systems, Minneapolis, Minnesota, USA) and MMPs (-1, -7, -8 and -9; R & D Systems) Expression levels were analyzed. At this time, the serum sample was used diluted to about 10 to 50 times.
  • assay buffer 200 ⁇ l per well was added to the microtiter plate and shaken for 10 minutes at room temperature, then the assay buffer was removed and 25 ⁇ l standard or control was added to the wells. Assay buffer (25 ⁇ L) was then added to each well and 25 ⁇ L of the corresponding matrix was added to the background, standard and control wells, respectively. Samples (25 ⁇ l) were then added to the sample wells and 25 ⁇ L beads were added to each well.
  • Two lasers are used, one laser is microparticle-specific and used to determine which analytes are detected, and the other laser is picorisrin-derived directly proportional to the amount of analyte bound. It was used to determine the magnitude of the signal.
  • the serum samples used were diluted 10-50 times with serum obtained from each patient in the test buffer.
  • the in-test accuracy for cathepsin D was 4.7% and the inter-test accuracy was 13.5%
  • the in-test accuracy was 2.1 to 10% and the inter-test accuracy was 8.3 to 15.6%
  • in-test accuracy was 4.2 to 11.1% and inter-test accuracy was 5.9 to 16.8%.
  • carbohydrate antigen 19-9 (CA 19-9) and fetal cancer antigen (CEA) levels were measured by ADVIA Centaur XP Immunoassay Systems (Siemens, Germany).
  • the threshold of each marker was defined for the purpose of obtaining maximum sensitivity and specificity.
  • FIG. 1 is a box whisker plot of serum levels of cathepsin D and MMP-7 in a training set comprising a healthy subject (H), a patient with chronic pancreatitis (CP) and a patient with pancreatic adenocarcinoma (PDAC).
  • H healthy subject
  • CP chronic pancreatitis
  • PDAC pancreatic adenocarcinoma
  • FIG. 1 shows that in PDAC patients, the levels of cathepsin D and MMP-7 were significantly higher compared to healthy subjects and patients with CP (medium level, 346 vs. 212 for cathepsin D).
  • ng / mL, p 0.0001; medium level, 3550 vs. 1350 pg / mL for MMP-7, p ⁇ 0.0001)
  • ROC curve analysis to establish sensitivity, specificity, area under curve (AUC) for cathepsin D, CA19-9 and MMP-7.
  • AUC area under curve
  • cathepsin D a sensitivity of 49.5% with a specificity of 88.6% showed an optimal fractionation capacity, providing a cut-off of 349 ng / mL for fractionating patients from control subjects.
  • the ROC curve for MMP-7 showed optimal (best sensitivity and specificity) at 71.6% sensitivity and 80.0% specificity, which showed a cut-off level of 2,050 pg / mL.
  • CA19-9 levels were significantly higher among patients compared to controls (121.2 vs 7.8 U / mL, P ⁇ 0.0001).
  • AUC 0.672, 95% CI: 0.598-0.740
  • 0.835, 95% CI: 0.772-0.886 the combination of CA19-9, cathepsin D and MMP-7 increased AUC compared to the CA19-9 monotherapy group in the training and validation set (FIG. 2).
  • 2 is a receiver manipulation characteristic (ROC) curve for diagnosing PDAC versus control patients. Diagnostic sensitivity for PDAC was enhanced by the combination of cathe
  • PPV positive predictive value
  • NPV speech prediction
  • Accuracy area under the curve
  • P value means significance level between each biomarker panel and CA19-9
  • the calibrated P value is calculated based on sensitivity under 80% specificity comparing CA19-9 and biomarker panel.
  • PPV positive predictive value
  • NPV speech prediction
  • Serum concentrations of cathepsin D and MMP-7 were significantly higher than those of the control group in the early stage PDAC patients (Table 4 and FIG. 3).
  • FIG. 3 is a box whisker plot of serum levels of cathepsin D and MMP-7 in healthy subjects (H), patients with chronic pancreatitis (CP) and patients with stage I or II pancreatic adenocarcinoma (PDAC).
  • H healthy subjects
  • CP chronic pancreatitis
  • PDAC pancreatic adenocarcinoma
  • PPV positive predictive value
  • NPV speech prediction
  • FIG. 4 shows serum levels of cathepsin D, MMP-7 and CA19-9 in patients and control groups with PDAC at various stages.
  • CA19-9, cathepsin D and MMP-7 can be used as useful biomarkers of pancreatic cancer.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Immunology (AREA)
  • Engineering & Computer Science (AREA)
  • Urology & Nephrology (AREA)
  • Biomedical Technology (AREA)
  • Hematology (AREA)
  • Chemical & Material Sciences (AREA)
  • Molecular Biology (AREA)
  • Physics & Mathematics (AREA)
  • Biochemistry (AREA)
  • Cell Biology (AREA)
  • Pathology (AREA)
  • Biotechnology (AREA)
  • Food Science & Technology (AREA)
  • Medicinal Chemistry (AREA)
  • General Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Microbiology (AREA)
  • General Health & Medical Sciences (AREA)
  • Oncology (AREA)
  • Hospice & Palliative Care (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Investigating Or Analysing Biological Materials (AREA)

Abstract

La présente invention concerne un réactif permettant de diagnostiquer l'adénocarcinome du pancréas, comprenant un moyen de mesure de la concentration sanguine du CA19-9, de la cathepsine D et de la métalloprotéinase matricielle 7. L'invention porte également sur un kit pour le diagnostic de l'adénocarcinome pancréatique contenant ledit réactif pour le diagnostic de l'adénocarcinome pancréatique, et sur un procédé permettant de fournir les informations nécessaires au diagnostic de l'adénocarcinome pancréatique au moyen dudit kit. Ce kit permet de réaliser un diagnostic précoce de l'adénocarcinome pancréatique et peut ainsi être largement utilisé pour traiter plus efficacement l'adénocarcinome pancréatique.
PCT/KR2012/007895 2011-09-28 2012-09-28 Kit pour le diagnostic de l'adénocarcinome pancréatique, comprenant des moyens de mesure du ca19-9, de la cathepsine d et la métalloprotéinase matricielle-7 Ceased WO2013048174A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR1020110098548A KR101358510B1 (ko) 2011-09-28 2011-09-28 카텝신 ｄ와 매트릭스 메탈로프로틴나제-7의 측정수단을 포함하는 췌장암 진단용 키트
KR10-2011-0098548 2011-09-28

Publications (2)

Publication Number Publication Date
WO2013048174A2 true WO2013048174A2 (fr) 2013-04-04
WO2013048174A3 WO2013048174A3 (fr) 2013-05-23

Family

ID=47996643

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2012/007895 Ceased WO2013048174A2 (fr) 2011-09-28 2012-09-28 Kit pour le diagnostic de l'adénocarcinome pancréatique, comprenant des moyens de mesure du ca19-9, de la cathepsine d et la métalloprotéinase matricielle-7

Country Status (2)

Country Link
KR (1) KR101358510B1 (fr)
WO (1) WO2013048174A2 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3159695A3 (fr) * 2013-06-20 2017-07-05 The Trustees of The University of Pennsylvania Procédé de diagnostic du cancer du pancréas
CN114250298A (zh) * 2020-09-23 2022-03-29 中国医学科学院北京协和医院 胰腺导管腺癌的dna甲基化标志物及其应用
WO2025064551A1 (fr) * 2023-09-19 2025-03-27 The Board Of Trustees Of The Leland Stanford Junior University Cathepsines à glycoprotéine active ciblées et procédés d'utilisation

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101665165B1 (ko) * 2013-12-04 2016-10-12 단국대학교 산학협력단 신규한 rna 앱타머 및 그의 용도
KR20150129932A (ko) 2014-05-12 2015-11-23 연세대학교 산학협력단 보체인자 b 단백질에 특이적으로 결합하는 항체를 포함하는 췌장암 진단용 키트

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5126243A (en) * 1982-08-09 1992-06-30 Centocor, Inc. Immunoassay for carbohydrate antigenic determinant

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3159695A3 (fr) * 2013-06-20 2017-07-05 The Trustees of The University of Pennsylvania Procédé de diagnostic du cancer du pancréas
CN114250298A (zh) * 2020-09-23 2022-03-29 中国医学科学院北京协和医院 胰腺导管腺癌的dna甲基化标志物及其应用
WO2025064551A1 (fr) * 2023-09-19 2025-03-27 The Board Of Trustees Of The Leland Stanford Junior University Cathepsines à glycoprotéine active ciblées et procédés d'utilisation

Also Published As

Publication number Publication date
WO2013048174A3 (fr) 2013-05-23
KR101358510B1 (ko) 2014-02-06
KR20130034505A (ko) 2013-04-05

Similar Documents

Publication Publication Date Title
KR101051435B1 (ko) 대장암 관련 마커를 이용한 대장암 진단 키트 및 이를 이용한 대장암 진단 방법
AU2004260083B2 (en) Markers for detection of gastric cancer
KR20160045547A (ko) 췌장암 진단용 조성물 및 이를 이용한 췌장암 진단방법
CN104039962A (zh) 乳腺癌诊断和预示的标志物
US11360093B2 (en) Colorectal cancer diagnostic composition, and method for detecting diagnostic marker
WO2013048174A2 (fr) Kit pour le diagnostic de l'adénocarcinome pancréatique, comprenant des moyens de mesure du ca19-9, de la cathepsine d et la métalloprotéinase matricielle-7
KR101478826B1 (ko) 신규한 대장암 진단용 마커 및 이를 이용한 대장암 진단 키트
KR102122452B1 (ko) 암의 진단용 조성물
KR20090029868A (ko) 체액 내 간암 마커로서의 아넥신 2 및 이를 이용한 간암진단 키트
WO2024117803A1 (fr) Nouveau biomarqueur pour prédire le pronostic du cancer du pancréas
WO2021100891A1 (fr) Composition et kit permettant de diagnostiquer le pronostic d'un cancer buccal
KR102881803B1 (ko) 췌장암의 진단용 조성물
KR102499664B1 (ko) 암의 진단용 조성물
KR20230160425A (ko) 췌장암의 진단용 조성물
KR102499678B1 (ko) 암의 진단용 조성물
KR102433986B1 (ko) 암의 진단용 조성물
KR102280360B1 (ko) 암의 진단용 조성물
KR102433983B1 (ko) 암의 진단용 조성물
KR102280672B1 (ko) 암의 진단용 조성물
KR102325742B1 (ko) 암의 진단용 조성물
WO2025198366A1 (fr) Nouveau biomarqueur de pronostic de lichen plan buccal et ses utilisations
WO2024219798A1 (fr) Composition pour diagnostic du cancer
KR20240158140A (ko) 췌장암의 진단용 조성물
WO2021172923A1 (fr) Composition pour le diagnostic du cancer
KR100931997B1 (ko) 간세포암 종양 마커로서의 ｋｌｋ-5 유전자 및 이를 이용한간세포암 진단 방법

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 12836486

Country of ref document: EP

Kind code of ref document: A2

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 12836486

Country of ref document: EP

Kind code of ref document: A2