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WO2022063156A1 - Biomarqueur du cancer du sein et son application - Google Patents

Biomarqueur du cancer du sein et son application Download PDF

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Publication number
WO2022063156A1
WO2022063156A1 PCT/CN2021/119819 CN2021119819W WO2022063156A1 WO 2022063156 A1 WO2022063156 A1 WO 2022063156A1 CN 2021119819 W CN2021119819 W CN 2021119819W WO 2022063156 A1 WO2022063156 A1 WO 2022063156A1
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breast cancer
akap4
cip2a
braf
brca2
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Chinese (zh)
Inventor
孙苏彭
朱得坤
隗啸南
杨盼盼
周静
康美华
孙立平
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Hangzhou Cancer Probe Biological Technology Co Ltd
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Hangzhou Cancer Probe Biological Technology Co Ltd
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    • 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
    • G01N33/57484—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites
    • G01N33/57488—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites involving compounds identifable in body fluids
    • 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
    • G01N33/57415—Specifically defined cancers of breast

Definitions

  • the present invention relates to the fields of biotechnology and medical diagnosis, in particular, the present invention relates to an autoantibody biomarker of breast cancer, an antigen combination for detecting the same, and their corresponding application in breast cancer detection.
  • Breast cancer is a malignant tumor originating from the breast, which is a common malignant tumor disease in women, with a high incidence in women between the ages of 40 and 55. In recent years, breast cancer has become younger, and the incidence rate among women over 20 years old is on the rise, which is presumed to be related to the improvement of early screening and diagnosis and treatment methods in recent years.
  • breast cancer Due to the lack of effective etiological preventive measures, early screening of breast cancer is an important secondary prevention method.
  • Breast cancer has traditionally been detected using imaging screening techniques, such as mammography, ultrasound, and breast MRI.
  • imaging screening techniques such as mammography, ultrasound, and breast MRI.
  • the detection results of these imaging screening techniques are related to the physician's experience and technical quality, and have shortcomings such as low resolution, unguaranteed specificity and sensitivity, and therefore need to develop more accurate, simple, low-risk and non-invasive sexual technical means to supplement or replace.
  • tumor antigen markers such as human epidermal growth factor receptor 2 (HER2) antigen and carbohydrate antigen 15-3 (CA15-3)
  • HER2 human epidermal growth factor receptor 2
  • CA15-3 carbohydrate antigen 15-3
  • detectable gene markers such as BRCA1 and BRCA2 or detection of cfDNA or MicroRNAs (miRNAs) have also been proposed, but there are also shortcomings such as lack of help in reducing breast cancer mortality or immature methods.
  • Autoantibodies are antibodies directed against one's own tissues, organs, cells and cellular components.
  • the exposure of tumor-associated antigens can be recognized by the human immune system, resulting in tumor-associated autoantibodies, and even maintain high levels of autoantibodies in peripheral blood, which can be sensitively detected by conventional technical means in the art.
  • autoantibodies produced by tumor antigens are good indicators for early diagnosis of tumors. Using tumor-induced autoantibodies to reflect the tumorigenesis mechanism and disease progression of patients is becoming a new target for early diagnosis and prognosis judgment of tumors. important direction.
  • breast cancer can be divided into three types pathologically: ER(+) positive, HER2(+) positive and triple negative breast cancer.
  • Triple-negative breast cancer defined as lack of expression of the estrogen receptor (ER), progesterone receptor (PR) and lack of overexpression or amplification of HER2, represents approximately 15% of breast cancer cases. This type of breast cancer has a poor prognosis and occurs more frequently in the younger population.
  • triple-negative breast cancer also has a high diversity and can be divided into 6 subtypes: basal-like (Basal-like, BL1 and BL2), mesenchymal (mesenchymal, M), mesenchymal-like stem cell-like ( mesenchymal stem-like, MSL), immunomodulatory (IM), luminal androgen receptor (LAR), and unspecified group (UNS).
  • Basal-like Basal-like, BL1 and BL2
  • mesenchymal mesenchymal-like stem cell-like
  • IM immunomodulatory
  • LAR luminal androgen receptor
  • UNS unspecified group
  • triple-negative breast cancer Early detection of triple-negative breast cancer is of great significance because triple-negative breast cancer easily develops into a lethal and rapidly proliferating tumor.
  • mammography is less sensitive for high breast density, and triple-negative breast cancer is often missed; while MRI is very sensitive, the false-positive rate is also very high. Therefore, non-invasive early detection of triple-negative breast cancer blood markers has important auxiliary significance in clinical application.
  • the traditional antigenic markers CEA, CA27.29 and CA15-3 have high sensitivity in advanced breast cancer, so they are not suitable for early detection of breast cancer, only for metastatic breast cancer Cancer monitoring.
  • Several potential blood markers have recently emerged as markers for early detection of triple-negative breast cancer.
  • serum apoC-I mRNA and protein is higher in triple-negative breast cancer than other types of breast cancer.
  • Serum apoC-I can be used for early detection and prognosis of triple-negative breast cancer (Diagnostic and prognostic significance of serum apolipoprotein).
  • CI in triple-negative breast cancer based on mass spectrometry. Song D. et. al. Cancer Biol Ther. 2016 Jun;17(6):635–647).
  • the present invention finally identifies a group of autoantibodies that can be used for screening breast cancer, especially early breast cancer, by detecting autoantibodies against different antigenic targets in the blood of breast cancer patients.
  • the autoantibody combination has sufficiently high sensitivity especially in early stage tumors, especially in the experimental Chinese population, and also has sufficiently high detection specificity.
  • an object of the present invention is to provide a biomarker for breast cancer, which is a combination of autoantibodies.
  • another object of the present invention is to provide a reagent for detecting the autoantibody combination, such as an antigen protein combination; and to provide the autoantibody combination or detection reagent in the preparation of breast cancer patients Use in products such as disease risk prediction, screening, prognosis assessment, treatment effect monitoring or recurrence monitoring.
  • Another object of the present invention is to provide a kit and a corresponding method for risk prediction, screening, prognosis evaluation, treatment effect monitoring or recurrence monitoring of breast cancer.
  • the present invention provides a biomarker for breast cancer
  • the biomarker is a combination of autoantibodies comprising at least three autoantibodies against the following tumor antigens: BRAF, CIP2A, AKAP4, GIPC1, BRCA2 , P53, SOX2, NY-ESO-1 and MUC-1.
  • the autoantibody combination comprises autoantibodies against the following tumor antigens, respectively: BRAF, CIP2A and AKAP4.
  • the autoantibody combination further comprises at least one of autoantibodies against the following tumor antigens: GIPC1, BRCA2, MUC-1, P53, SOX2 and NY-ESO-1, respectively.
  • the autoantibody combination preferably includes at least one, at least two or at least three of the autoantibodies against the following tumor antigens: GIPC1, BRCA2, MUC-1 and P53.
  • the autoantibody combination includes autoantibodies against the following tumor antigens: BRCA2 and/or MUC-1; alternatively: GIPC1 and/or BRCA2.
  • the autoantibody combination comprises autoantibodies against the following tumor antigens, respectively:
  • BRAF BRAF, CIP2A, AKAP4, GIPC1, BRCA2, P53, SOX2, NY-ESO-1, MUC-1.
  • the autoantibody is an autoantibody in whole blood, serum, plasma, tissue or cells, interstitial fluid, cerebrospinal fluid or urine of a subject; wherein preferably, the tissue or cell is breast tissue or Cells, breast cancer tissue or cells, or adjacent breast cancer tissue or cells.
  • the subject is a mammal, preferably a primate, more preferably a human.
  • the autoantibody is IgA (eg IgAl, IgA2), IgM or IgG (eg IgGl, IgG2, IgG3, IgG4).
  • the breast cancer includes non-invasive cancer and invasive cancer.
  • the non-invasive carcinoma includes, for example, ductal carcinoma in situ, lobular carcinoma in situ, etc.; wherein the invasive carcinoma includes, for example, invasive ductal carcinoma, invasive micropapillary carcinoma, invasive lobular carcinoma and mucinous carcinoma.
  • the breast cancer includes triple negative and non-triple negative breast cancer.
  • the combination of biomarkers ie autoantibodies
  • a sample eg plasma or serum
  • autoantibodies can be used interchangeably with "positive” or “negative”; it is a routine technique in the art to judge this.
  • Detection can be performed, for example, by antigen-antibody-specific reactions between tumor-associated antigens that result in the appearance of any autoantibodies in the combination.
  • the present invention also provides a reagent for detecting the biomarkers of the present invention.
  • the reagents may be reagents for enzyme-linked immunosorbent assay (ELISA), protein/peptide chip detection, immunoblotting, microbead immunoassay, or microfluidic immunoassay, and the like.
  • ELISA enzyme-linked immunosorbent assay
  • the reagents are used to detect the biomarkers of the invention by antigen-antibody reaction, eg by ELISA or fluorescence or chemiluminescence immunodetection.
  • the agent may be an antigenic protein combination comprising at least three tumor antigens selected from the group consisting of BRAF, CIP2A, AKAP4, GIPC1, BRCA2, P53, SOX2, NY-ESO-1 and MUC-1 .
  • the antigen-protein combination includes the following tumor antigens: BRAF, CIP2A and AKAP4.
  • the antigen-protein combination further includes at least one of the following tumor antigens: GIPC1, BRCA2, MUC-1, P53, SOX2 and NY-ESO-1.
  • the antigen-protein combination preferably includes at least one, at least two or at least three of the following tumor antigens: GIPC1, BRCA2, MUC-1 and P53.
  • the antigen-protein combination includes the following tumor antigens: BRCA2 and/or MUC-1; or: GIPC1 and/or BRCA2.
  • the antigen-protein combination includes the following tumor antigens:
  • BRAF BRAF, CIP2A, AKAP4, GIPC1, BRCA2, P53, SOX2, NY-ESO-1, MUC-1.
  • the present invention provides the use of the biomarker or reagent in the preparation of a product for risk prediction, screening, prognosis evaluation, treatment effect monitoring or recurrence monitoring of breast cancer.
  • the breast cancer includes non-invasive cancer and invasive cancer.
  • the non-invasive carcinoma includes, for example, ductal carcinoma in situ, lobular carcinoma in situ, etc.; wherein the invasive carcinoma includes, for example, invasive ductal carcinoma, invasive micropapillary carcinoma, invasive lobular carcinoma and mucinous carcinoma.
  • the breast cancer includes triple negative and non-triple negative breast cancer.
  • the product is a kit; more preferably, the kit is used for enzyme-linked immunosorbent assay (ELISA), protein/peptide chip detection, western blotting, bead immunoassay or microfluidic immunoassay
  • the kit is used to detect the biomarker through antigen-antibody reaction, such as an ELISA kit or a fluorescence or chemiluminescence immunodetection kit.
  • the present invention provides a kit comprising the reagent of the present invention.
  • the kit may be a kit for enzyme-linked immunosorbent assay (ELISA), protein/peptide chip detection, immunoblotting, microbead immunoassay, or microfluidic immunoassay, and the like.
  • ELISA enzyme-linked immunosorbent assay
  • the kit is used to detect the biomarkers of the present invention through antigen-antibody reaction, such as an ELISA kit or a fluorescence or chemiluminescence immunodetection kit.
  • the kit is an enzyme-linked immunosorbent assay (ELISA) detection kit. That is, using the kit, whether the autoantibody biomarker is positive in the sample of the subject is detected by enzyme-linked immunosorbent assay.
  • the kit may also include other components required for ELISA detection of autoantibody biomarkers, which are well known in the art.
  • the antigenic protein in the kit can be linked with a tag peptide, such as His tag, streptavidin tag, Myc tag; for another example, the kit can include a solid phase carrier, such as with an immobilized antigen. Protein microwell carriers, such as microtiter plates; or microbeads or magnetic bead solid-phase carriers.
  • It can also include adsorbed proteins for immobilizing antigen proteins on solid supports, dilutions of blood such as serum, washing solutions, secondary antibodies with enzyme-labeled or fluorescent or chemiluminescent substances, chromogenic solutions, Stop solution, etc.
  • concentration of the corresponding antibody in the body fluid is detected by the principle that the antigen protein indirectly or directly coated on the surface of the solid phase carrier reacts with the antibody in serum/plasma/tissue fluid to form an antigen-antibody complex.
  • the present invention provides a method for disease risk prediction, screening, prognosis assessment, treatment effect monitoring or recurrence monitoring of breast cancer, comprising the following steps:
  • the quantification includes detecting each autoantibody in the autoantibody combination using the reagent provided by the present invention (ie, the antigen-protein combination) or a kit comprising the reagent.
  • the subject is a mammal, preferably a primate mammal, more preferably a human.
  • the breast cancer includes non-invasive cancer and invasive cancer.
  • the non-invasive carcinoma includes, for example, ductal carcinoma in situ, lobular carcinoma in situ, etc.
  • the invasive carcinoma includes, for example, invasive ductal carcinoma, invasive micropapillary carcinoma, invasive lobular carcinoma and mucinous carcinoma.
  • the breast cancer includes triple negative and non-triple negative breast cancer.
  • the sample is whole blood, serum, plasma, tissue or cells, interstitial fluid, cerebrospinal fluid or urine of the subject; wherein preferably, the tissue or cells are breast tissue or cells, breast cancer tissue Or cells or adjacent tissue or cells of breast cancer.
  • the reference threshold may be a reference level from a healthy person or a healthy population; for example, it may be defined as the mean plus 2 standard deviations of a population confirmed by physical examination to be free of cancer.
  • the present invention provides a novel biomarker of breast cancer, which is a completely new group of tumor autoantibodies.
  • These autoantibodies all have a high positive detection rate in the early stage of breast cancer, and have a separate positive contribution rate; and, according to the analysis of breast cancer staging, the autoantibody combination of the present invention has good detection sensitivity and sufficiently high The detection specificity can reach more than 50% sensitivity even in the early stage of breast cancer.
  • experiments have proved that the autoantibody combination of the present invention has similar detection sensitivity to triple-negative and non-triple-negative breast cancer, both reaching more than 50%.
  • Figure 1 is a scatter plot of the level distribution of each tumor autoantibody in the tumor group and the control group.
  • Figure 2 shows the results of sensitivity analysis of autoantibody combinations for triple-negative and non-triple-negative breast cancer patients.
  • the term "antigen” or the term “antigenic protein” are used interchangeably.
  • the following experimental procedures or definitions are involved in the present invention. It should be noted that the present invention can also be implemented using other conventional techniques in the art, and is not limited to the following experimental operations.
  • the cDNA fragment of tumor antigen was cloned into PET28(a) expression vector containing 6XHis tag.
  • a streptavidin protein or an analog (a biotin-binding tag protein) is introduced.
  • the obtained recombinant expression vector was transformed into E. coli for expression.
  • the protein expressed in the supernatant was purified by Ni-NTA affinity column and ion column.
  • the protein is denatured with 6M guanidine hydrochloride, renatured and folded according to standard methods in vitro, and then purified by Ni-NTA affinity column through 6XHis tag to obtain the antigenic protein.
  • Plasma or serum of breast cancer patients was collected when the patients were initially diagnosed with breast cancer and had not received any radiotherapy, chemotherapy and surgery. Plasma or serum were prepared according to standard clinical procedures and stored in a -80°C freezer for long-term storage.
  • the concentration of autoantibodies in the samples was quantified by enzyme-linked immunosorbent assay (ELISA).
  • Microwells are pre-coated with biotinylated bovine serum albumin (BSA).
  • BSA biotinylated bovine serum albumin
  • Serum or plasma samples were diluted 1:110 with phosphate buffer and added to microwells for reaction (50 mL/well). After washing unbound serum or plasma fractions with wash solution, horseradish peroxidase (HRP)-conjugated anti-human IgG was added to each well for the reaction. Then the reaction substrate TMB (3,3',5,5'-tetramethylbenzidine) was added for color development. A stop solution (1N HCl) was added, and the absorbance at 450nm was single-spectrum for reading (OD) by a microplate reader. Serum autoantibody concentrations were quantified using a standard curve.
  • the cutoff value for autoantibodies was defined as the mean plus 2 standard deviations (SD) or the mean plus 3 standard deviations (SD) of the detected absorbance values in a control normal population confirmed by physical examination to be free of cancer.
  • the cutoff value of each autoantibody is determined according to the following principles: 1. In the case of using two different values (mean plus two standard deviations and mean plus three standard deviations) as reference thresholds, each autoantibody pair The detection specificity of the control normal population is 95% or above; 2. Under the condition that the two different values are used as reference thresholds, the specificity of each autoantibody to the control normal population and the detection of breast cancer are obtained. For the sensitivity of the cancer patient population, the sum of the two is calculated, and the value when the sum is larger is selected as the determined cutoff value of the autoantibody.
  • a positive reaction was defined as a quantification of the level of autoantibodies in the sample, which was compared to the cutoff value, with a ⁇ cutoff value of positive; correspondingly, a negative reaction was defined as a ⁇ cutoff value of negative.
  • the results of multiple autoantibodies are combined to determine the predictive effect.
  • the rule is: if multiple autoantibodies are detected in the sample, as long as one or more of the autoantibodies are positive, the result of the antibody combination is judged to be positive; and if all the autoantibodies are negative, the result of the antibody combination is judged to be negative.
  • Sensitivity Among all breast cancer cases diagnosed by the gold standard, the proportion of cases with positive autoantibody or autoantibody combination test results in all diseased cases.
  • ER estrogen receptor
  • PR progesterone receptor
  • HER2 human epidermal growth factor receptor 2
  • ER 1% to 50% of positive staining tumor cells
  • the PR expression levels are artificially grouped as:
  • PR(-) PR negative
  • PR (medium): 1% to 10% of positive staining tumor cells
  • PR(high) >10% of positively stained tumor cells.
  • HER2 on the surface of breast cancer tissue cells was detected by immunohistochemistry, and the results were HER2(0) to HER2(3+). More than 10% of cells showed intense staining of the intact membrane as 3+. Expression levels ranging from 0 to 1+ were considered negative for HER2 expression. If the result is 2+, the expression level is critical. In this case, in situ hybridization will be used to further detect HER2 gene amplification. When single-copy HER2 gene > 6 or HER2/CEP17 ratio > 2.0, HER2 expression is positive , otherwise negative.
  • Serum specimens from breast cancer patients were obtained from Shanghai Cancer Hospital, and healthy individuals were from 4 different hospitals and physical examination centers. Serum from all breast cancer patients was collected when the patient was initially diagnosed with breast cancer and had not received any radiotherapy, chemotherapy and surgery, and was stored in a -80 degree refrigerator.
  • the patient information used for the discovery cohort is shown in Table 1.
  • Table 1 Discovery cohort patient characteristics table
  • breast cancer antigens were selected, expressed and purified, and then coated on the surface of 96-well plate. After blocking, they were reacted with breast cancer serum or normal control serum diluted 1:110 times, and then reacted with anti-human IgG antibody-HRP horseradish hydrogen peroxide. Enzyme reaction, then color reaction, and detection with microplate reader OD450nm wavelength. Table 2 shows the detection sensitivity and specificity of each antigen.
  • the autoantibodies corresponding to the above 25 antigens were sorted in the following three layers:
  • the validation cohort included 100 newly collected breast cancer patients (9 ductal carcinoma in situ, 87 invasive ductal carcinoma, 1 invasive micropapillary carcinoma, 1 invasive lobular carcinoma, 2 mucinous carcinomas), and Validation of antibody markers was carried out in 73 random physical examination populations collected from 4 different hospitals. Patient information is shown in Table 5.
  • Table 5 Validation cohort patient characteristics table (not targeting advanced patients, so the validation cohort has no stage IV)
  • the level distribution of each tumor autoantibody in the tumor group and the control group was represented by a scatter plot (see Figure 1). Due to the different strengths of the immune systems of tumor patients and the diversity of tumor production mechanisms, the distribution sensitivity of a single tumor autoantibody in tumor patients is low, usually only between 5% and 20%.
  • the distribution of antibody levels of tumor autoantibodies in the tumor group and the control group was statistically analyzed using the Mann Whitney test, and it was found that the level distribution of autoantibodies against tumor antigens BRAF, CIP2A and BRCA2 was significantly different between the tumor group and the control group (p ⁇ 0.05); while the level distribution of autoantibodies against tumor antigens AKAP4, GIPC1, MUC1, SOX2, P53 and NY-ESO-1 was not significantly different between the tumor group and the control group. It is speculated that the main reason may be that most tumor patients have negative tumor autoantibody levels, and their antibody levels are not significantly different from those of the normal control group.
  • the detection sensitivity and specificity of 9 tumor autoantibody markers in the sera of 100 breast cancer patients and 73 healthy control sera from the validation cohort are shown in Table 6.
  • the specificity of each marker was 97.3% or above, and the sensitivity was between 6 and 17%.
  • the combination of 4 different antibodies excluding the three autoantibodies against BRAF, CIP2A and AKAP4 was 28-32% sensitive and 91.8-93.1% specific.
  • the sensitivity and specificity of the panel including autoantibody markers against 9 tumor antigens BRAF, CIP2A, AKAP4, GIPC1, BRCA2, P53, SOX2, MUC1 and NY-ESO-1 were 53% and 84.9%, respectively, in the validation cohort .
  • a combination of autoantibody markers against 9 tumor antigens BRAF, CIP2A, AKAP4, GIPC1, BRCA2, P53, SOX2, MUC1 and NY-ESO-1 was selected for sensitivity analysis of different stages and types of breast cancer.
  • the validation cohort included 100 breast cancer patients, including 9 ductal carcinoma in situ (DCIS), 87 invasive ductal carcinoma (IDC), 1 invasive lobular carcinoma (ILC), 3 invasive Specific breast cancers (1 invasive micropapillary carcinoma, 2 mucinous carcinomas), different stages and subtypes were analyzed for sensitivity of tumor autoantibody combinations to detection.
  • DCIS 9 ductal carcinoma in situ
  • IDC 87 invasive ductal carcinoma
  • ILC invasive lobular carcinoma
  • 3 invasive Specific breast cancers (1 invasive micropapillary carcinoma, 2 mucinous carcinomas), different stages and subtypes were analyzed for sensitivity of tumor autoantibody combinations to detection.
  • stage 0 The majority of breast cancer patients in the validation cohort were stage 0, I and II, accounting for 84%, of which 9 were stage 0 with a sensitivity of 56% and 29 patients with stage I had a sensitivity of 52 %; 46 stage II patients with a sensitivity of 56%; 5 stage III patients with a sensitivity of 80%.
  • the results are shown in Table 8.
  • Ductal Carcinoma In situ arises in the ducts of the breast and is not aggressive. It accounts for about 20% of newly discovered breast cancer cases.
  • Invasive Ductal Carcinoma (IDC) is the most common type of breast cancer, accounting for about 80% of newly discovered breast cancer cases. It arises in the ducts of the breast, but has invaded other tissues of the breast and can be classified. There are five different types: tubular, medullary, mucous, papillary and cribriform.
  • IDC Invasive lobular carcinoma
  • Tumors develop in the lobules that produce milk and invade other tissues of the breast. It accounts for the proportion of newly identified cases of invasive breast cancer. about 10%.
  • the expression levels of the three hormone receptors ER, PR, and HER2 in breast cancer tumor cells have important effects on the growth of tumor cells and the choice of treatment options.
  • the expression levels of three hormone receptors, ER, PR, and HER2 in breast cancer tumor pathological sections were analyzed and classified, and whether the expression levels of ER, PR, and HER2 affected the detection of tumor autoantibodies.
  • 12 were triple-negative breast cancer patients, and the sensitivity of the combination of tumor autoantibodies was 58.3%, while the sensitivity of the combination of tumor autoantibodies was 58.3% in the remaining 88 patients with non-triple-negative breast cancer. 52.2%.
  • the tumor autoantibody combination was similar in sensitivity in triple-negative and non-triple-negative patients in detecting patients with early breast cancer. The results are shown in Figure 2.

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Abstract

La présente invention concerne un biomarqueur du cancer du sein. Le biomarqueur est une combinaison d'auto-anticorps comprenant au moins trois auto-anticorps ciblant respectivement les antigènes tumoraux suivants : BRAF, CIP2A, AKAP4, GIPC1, BRCA2, P53, SOX2, NY-ESO-1 et MUC-1. Un dépistage précoce du cancer du sein peut être effectué en testant le biomarqueur. La présente invention concerne également une combinaison de protéines antigéniques pour tester le biomarqueur, un kit contenant la combinaison de protéines antigéniques, ainsi qu'un procédé de test ou de diagnostic correspondant.
PCT/CN2021/119819 2020-09-23 2021-09-23 Biomarqueur du cancer du sein et son application Ceased WO2022063156A1 (fr)

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CN115372616B (zh) * 2022-07-15 2023-09-15 杭州凯保罗生物科技有限公司 胃癌相关的生物标志物及其应用
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