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WO2019021654A1 - Marqueur de pronostic du cancer du pancréas, kit de diagnostic du pronostic du cancer du pancréas et procédé de prédiction du pronostic du cancer du pancréas - Google Patents

Marqueur de pronostic du cancer du pancréas, kit de diagnostic du pronostic du cancer du pancréas et procédé de prédiction du pronostic du cancer du pancréas Download PDF

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WO2019021654A1
WO2019021654A1 PCT/JP2018/022186 JP2018022186W WO2019021654A1 WO 2019021654 A1 WO2019021654 A1 WO 2019021654A1 JP 2018022186 W JP2018022186 W JP 2018022186W WO 2019021654 A1 WO2019021654 A1 WO 2019021654A1
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amino acid
acid sequence
pancreatic cancer
protein
seq
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恵介 谷内
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Kochi University NUC
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • G01N33/575—

Definitions

  • the present invention relates to a cancer marker capable of predicting the "prognosis" of a patient with pancreatic cancer, a kit for prognosis of pancreatic cancer for detecting the marker, and a method for predicting the prognosis of pancreatic cancer using the marker .
  • Pancreatic cancer has been on the rise in recent years, and Japan is the fourth leading cause of cancer death after lung cancer, gastric cancer and colon cancer, and there are 39,000 deaths annually from pancreatic cancer.
  • Pancreatic cancer is said to have the worst prognosis among cancers, and the cause is that early detection is difficult because pancreatic cancer is a retroperitoneal organ, and the motility of pancreatic cancer cells is extremely high. It immediately infiltrates surrounding blood vessels, digestive tracts, nerves, etc., and also metastasizes to nearby lymph nodes, distantly metastasizes to liver etc., and the like.
  • Pancreatic cancer is a representative of refractory cancer and surgery with early detection is the only way to increase survival.
  • the 5-year survival rate is a very low value of 5 to 10% in the whole of pancreatic cancer patients.
  • Reference Material 1 shows the 5-year survival rate of pancreatic cancer including postoperative cases, Stage IA: 31-39%, Stage IB: 22-27%, Stage IIA: 16-25%, Stage IIB: 8-10% Stage III: 0-7% Stage IV: 0-4% (Reference Material 1: Lancet Oncol 2013; 14: pp. 476-85).
  • the 5-year survival rate that is, the prognosis of patients with pancreatic cancer, rapidly deteriorates from stage IIA to stage IIB.
  • Patent Document 1 discloses a diagnostic marker for pancreatic cancer and intraductal papillary mucinous neoplasms characterized in that it contains one or more proteins selected from the group consisting of secretoglobin, family 1D, member 2 and podocalyxin-like proteins. It is disclosed.
  • Non-Patent Document 1 describes that POD XL is a diagnostic tool for pancreatic ductal adenocarcinoma and the like.
  • Typical treatments for cancer include surgical treatment, chemotherapy, radiation treatment, etc.
  • the 5-year survival rate of pancreatic cancer decreases sharply above stage IIB.
  • stage IIA, stage IIB, and stage III cases among the surgery indication cases uniform chemotherapy is performed regardless of the stage. If there is a method that can predict the prognosis of patients with pancreatic cancer with higher accuracy than prediction based on stage, for example, depending on the patient's needs, more potent chemotherapy is selected for good prognosis group, and reserve failure group.
  • the above-mentioned diagnostic marker known from the prior art is for determining the presence or absence and stage of cancer, and a "prognostic marker for pancreatic cancer" having high sensitivity and specificity has not been put into practical use yet.
  • an object of the present invention is to provide a cancer marker that has high sensitivity and specificity, and can predict the "prognosis" of pancreatic cancer patients.
  • the inventor of the present invention is a prognostic marker including a combination of the protein ITGB1 and the protein PODXL and / or the protein BCL7B, which is also superior in sensitivity to the stages III to IV.
  • the present invention has been completed by finding that the prognosis of pancreatic cancer patients can be predicted by
  • the protein ITGB1 Prognostic marker for pancreatic cancer characterized in that it comprises, in combination with protein PODXL and / or protein BCL7B.
  • the protein ITGB1 has an amino acid sequence of any one of the following (1) to (3): (1) the amino acid sequence of SEQ ID NO: 1; (2) an amino acid sequence having a deletion, substitution and / or addition of one or more and 10 or less amino acids in the amino acid sequence of SEQ ID NO: 1; (3) An amino acid sequence having 95% or more homology to the amino acid sequence set forth in SEQ ID NO: 1.
  • an antibody against the protein ITGB1 A kit for prognosis of pancreatic cancer, comprising an antibody against protein PODXL and / or an antibody against protein BCL7B.
  • [6] A kit for prognostic diagnosis of pancreatic cancer according to [5], wherein the protein ITGB1 has an amino acid sequence of any one of the following (1) to (3): (1) the amino acid sequence of SEQ ID NO: 1; (2) an amino acid sequence having a deletion, substitution and / or addition of one or more and 10 or less amino acids in the amino acid sequence of SEQ ID NO: 1; (3) An amino acid sequence having 95% or more homology to the amino acid sequence set forth in SEQ ID NO: 1.
  • a kit for prognostic diagnosis of pancreatic cancer according to [5] or [6], wherein said protein PODXL has an amino acid sequence of any one of the following (4) to (6): (4) the amino acid sequence of SEQ ID NO: 2; (5) an amino acid sequence having a deletion, substitution and / or addition of one or more and 25 or less amino acids in the amino acid sequence set forth in SEQ ID NO: 2; (6) An amino acid sequence having 95% or more homology to the amino acid sequence set forth in SEQ ID NO: 2.
  • [8] A kit for prognostic diagnosis of pancreatic cancer according to any one of [5] to [7], wherein the protein BCL7B has an amino acid sequence of any one of the following (7) to (9): (7) the amino acid sequence of SEQ ID NO: 3; (8) an amino acid sequence having a deletion, substitution and / or addition of one or more and 10 or less amino acids in the amino acid sequence set forth in SEQ ID NO: 3; (9) An amino acid sequence having 95% or more homology to the amino acid sequence set forth in SEQ ID NO: 3.
  • a method for predicting the prognosis of pancreatic cancer comprising Measuring the score or concentration of immunohistological staining in a sample of protein ITGB1 and one or more proteins selected from the group consisting of protein PODXL and protein BCL7B.
  • the protein ITGB1 has an amino acid sequence of any one of the following (1) to (3): (1) the amino acid sequence of SEQ ID NO: 1; (2) an amino acid sequence having a deletion, substitution and / or addition of one or more and 10 or less amino acids in the amino acid sequence of SEQ ID NO: 1; (3) An amino acid sequence having 95% or more homology to the amino acid sequence set forth in SEQ ID NO: 1.
  • the protein ITGB1 has an amino acid sequence of any one of the following (1) to (3): (1) the amino acid sequence of SEQ ID NO: 1; (2) an amino acid sequence having a deletion, substitution and / or addition of one or more and 10 or less amino acids in the amino acid sequence of SEQ ID NO: 1; (3) An amino acid sequence having 95% or more homology to the amino acid sequence set forth in SEQ ID NO: 1.
  • a cancer marker having high sensitivity and specificity, and capable of predicting the "prognosis" of a pancreatic cancer patient is provided.
  • pancreatic cancer cases can be further subdivided into good prognosis groups and poor prognosis groups, and more detailed medical care can be provided according to the patient's situation, and as a result, it can contribute to the improvement of prognosis of pancreatic cancer patients. It becomes possible.
  • the present invention can be useful clinical information in digestive medicine and digestive surgery which is a medical treatment area of pancreatic cancer.
  • the prognostic curve of 102 pancreatic cancer postoperative cases is shown.
  • the Kaplan-Meier curve of Vav3 is shown.
  • An example (low expression) of the pathological staining image of Vav3 is shown.
  • An example (high expression) of the pathological staining image of Vav3 is shown.
  • the Kaplan-Meier curve of PODXL is shown.
  • An example (low expression) of the pathological staining image of PODXL is shown.
  • An example (high expression) of the pathological staining image of PODXL is shown.
  • Kaplan-Meier curve of CCDC 88A is shown.
  • An example (low expression) of a pathological staining image of CCDC88A is shown.
  • An example (high expression) of a pathological staining image of CCDC88A is shown.
  • the Kaplan-Meier curve of SCGB1D2 is shown.
  • An example (low expression) of a pathological staining image of SCGB1D2 is shown.
  • An example (high expression) of a pathological staining image of SCGB1D2 is shown.
  • the Kaplan-Meier curve of BCL7B is shown.
  • An example (low expression) of a pathological staining image of BCL7B is shown.
  • An example (high expression) of a pathological staining image of BCL7B is shown.
  • the Kaplan-Meier curve of ARHGEF 4 is shown.
  • An example (low expression) of the pathological staining image of ARHGEF4 is shown.
  • An example (high expression) of the pathological staining image of ARHGEF4 is shown.
  • the Kaplan-Meier curve of WASF 2 is shown.
  • An example (low expression) of a pathological staining image of WASF2 is shown.
  • An example (high expression) of a pathological staining image of WASF2 is shown.
  • the Kaplan-Meier curve of ITGB 1 is shown.
  • An example (low expression) of a pathological staining image of ITGB1 is shown.
  • An example (high expression) of a pathological staining image of ITGB1 is shown.
  • Prognostic Markers for Pancreatic Cancer target prognosis of pancreatic cancer patients. As described above, if the cases of pancreatic cancer patients can be subdivided into good prognosis groups and poor prognosis groups with high accuracy, it is considered extremely useful for selection of treatment methods considering patient QOL.
  • Prognostic markers comprising the combination of the protein ITGB1 and the protein PODXL and / or the protein BCL7B, as examined by the inventor, surprisingly predict the prognosis of patients with pancreatic cancer with a higher accuracy than predicted based on cancer stage It turned out that it can be done.
  • the protein ITGB1, the protein BCL7B, and the protein PODXL which was conventionally considered to be effective as a diagnostic marker for pancreatic cancer, have significant results superior to the cancer stage for predicting the prognosis of pancreatic cancer patients, even when used alone as markers. Although it could not be obtained, it was surprising that, contrary to the conventional technical common sense, significant results were obtained for the first time by combining these.
  • the prognostic markers for pancreatic cancer according to the present invention include the protein ITGB1 (hereinafter abbreviated as “ITGB1”), the protein PODXL (hereinafter abbreviated as “PODXL”) and / or the protein BCL7B (hereinafter referred to as "BCL7B”) In combination with the above.
  • ITGB1 protein ITGB1
  • PODXL protein PODXL
  • BCL7B protein BCL7B
  • prognosis of pancreatic cancer refers to the prognosis of the patient before pancreatic cancer surgery before the pancreatic cancer tissue is removed by surgery, and the prognosis of the patient after pancreatic cancer surgery after the pancreatic cancer tissue is removed by surgery.
  • the prognostic marker for pancreatic cancer, the prognostic kit for pancreatic cancer, and the method for predicting the prognosis of pancreatic cancer according to the present invention are particularly useful for predicting the prognosis of patients after pancreatic cancer surgery.
  • the above "sensitivity” is sensitivity to the prognosis of pancreatic cancer patients.
  • the probability of being judged good in prognosis is high, and in patients with poor prognosis of pancreatic cancer, the probability of being judged bad in prognosis is Say high.
  • the above-mentioned “specificity” is the specificity for the prognosis of pancreatic cancer patients, and while there is a strong correlation between the amount of the above-mentioned protein and the prognosis of pancreatic cancer patients, Amount refers to no or low correlation with prognosis of patients who have undergone surgery for benign disease or cancer other than pancreatic cancer.
  • classification by cancer stage is widely used to indicate the degree of progression of pancreatic cancer.
  • the stage of pancreatic cancer is divided into four stages I to IV, and the stage includes the size of the tumor, adjacent organs (eg, duodenum, bile duct, portal system It is determined based on the presence or absence of infiltration into the mesenteric artery etc., the presence or absence of lymph node metastasis, the presence or absence of distant metastasis, etc. As the stage increases in number, it indicates that pancreatic cancer is more advanced, and, for example, a case in which pancreatic cancer has progressed and there is distant metastasis is stage IV.
  • adjacent organs eg, duodenum, bile duct, portal system
  • cancer stage is treated as the most important clinical information as treatment selection and patient prognostic factor, but with the prognostic marker according to the present invention, pancreatic cancer with higher accuracy than prediction based on this cancer stage
  • the ability to predict a patient's prognosis is extremely surprising in the art.
  • ITGB1 belongs to the integrin family and is a cell adhesion receptor on the cell surface. Although ITGB1 links the extracellular matrix with the intracellular skeleton and is involved in cell-cell adhesion, its specific function on cancer cells is poorly understood, including pancreatic cancer.
  • PODXL belongs to the CD34-related family, and is a glycoprotein involved in the control of canceration in addition to the development and differentiation of blood cells, cell adhesion and morphogenesis.
  • BCL7B has no known domain and its function is unknown. Therefore, it is unclear what family it belongs to, and it is impossible at this time to guess the function. It was identified in the research conducted by the present inventor to elucidate the novel invasion / metastasis mechanism of pancreatic cancer cells, and is currently under function analysis.
  • the ITGB1 has the amino acid sequence of SEQ ID NO: 1
  • the PODXL has the amino acid sequence of SEQ ID NO: 2
  • the BCL7B has the amino acid sequence of SEQ ID NO: 3.
  • the above-mentioned ITGB1, PODXL and BCL7B may have a mutation called single nucleotide polymorphism in humans, and such a mutant protein is also useful as a prognostic marker according to the present invention. That is, the scope of the present invention includes cases where the above prognostic marker has the following amino acid sequence.
  • Amino acid sequence (1) amino acid sequence described in SEQ ID NO: 1; Amino acid sequence (2): amino acid sequence of a protein having a deletion, substitution and / or addition of one or more and 10 or less amino acids in the amino acid sequence set forth in SEQ ID NO: 1 and found in body fluid of pancreatic cancer patients; Amino acid sequence (3): amino acid sequence of a protein having 95% or more homology to the amino acid sequence set forth in SEQ ID NO: 1 and found in the fluid of a patient with pancreatic cancer; Amino acid sequence (4): amino acid sequence described in SEQ ID NO: 2; Amino acid sequence (5): amino acid sequence of a protein having a deletion, substitution and / or addition of one or more amino acids and 25 or less amino acids in the amino acid sequence set forth in SEQ ID NO: 2 and found in body fluid of pancreatic cancer patients; Amino acid sequence (6): amino acid sequence of a protein having 95% or more homology to the amino acid sequence set forth in SEQ ID NO: 2 and found in the body
  • the number of deletions, substitutions and / or additions in the amino acid sequence (2) is preferably 8 or less, more preferably 5 or less, still more preferably 3 or less, still more preferably 1 or 2.
  • the number of deletions, substitutions and / or additions is preferably 20 or less, 15 or less or 10 or less, more preferably 8 or less, 6 or less, 5 or less or 4 or less, 1 or 2 Is even more preferred.
  • the number of deletions, substitutions and / or additions in the amino acid sequence (8) is preferably 8 or less, more preferably 5 or less, still more preferably 3 or less, still more preferably 1 or 2.
  • sequence identity in the above amino acid sequence (3) is preferably 96% or more or 98% or more, more preferably 99.0% or more, 99.2% or more or 99.5% or more, 99.6% or more 99.8 or more is still more preferable.
  • sequence identity in the above amino acid sequence (6) is preferably 96% or more or 98% or more, more preferably 99.0% or more, 99.2% or more or 99.5% or more, 99.6% or more 99.8 or more is still more preferable.
  • sequence identity in the above amino acid sequence (9) is preferably 96% or more or 98% or more, more preferably 99.0% or more, 99.2% or more or 99.5% or more, 99.6% or more 99.8 or more is still more preferable.
  • the amino acid sequence consists of the amino acid sequence of SEQ ID NO: 1, the amino acid sequence of SEQ ID NO: 2, and the amino acid sequence of SEQ ID NO: 3, respectively.
  • a marker containing a combination of ITGB1 and PODXL, or a marker containing a combination of ITGB1 and BCL7B is preferable. If these combinations are used, they exhibit hazard ratios superior to those of stages III and IV of pancreatic cancer, so that the sensitivity and specificity further improve.
  • sample acquisition process a sample is acquired from a subject.
  • the sample refers to a processed body fluid such as serum or plasma, in addition to the body fluid of the subject such as pancreatic cancer tissue, blood, lymph fluid, urine or the like extracted by surgery.
  • a pancreatic cancer tissue removed by surgery is preferable.
  • Measurement step of ITGB1 and PODXL and / or BCL7B In this step, it is in a sample of ITGB1 and one or more proteins selected from the group consisting of PODXL and BCL7B (preferably, a pancreatic cancer tissue removed by surgery) The staining score or concentration by immunohistological staining is measured.
  • the amount to be measured is not only the absolute amount of one or more proteins selected from the group consisting of ITGB1 and PODXL and BCL7B in a predetermined amount of sample, but also the staining score or concentration by immunohistological staining of these proteins in the sample It may be
  • the measuring means is not particularly limited as long as it can measure the amount of ITGB1, PODXL and BCL7B in the sample.
  • a staining score by immunohistological staining using a pancreatic cancer tissue removed by surgery or a spectrophotometric analysis method such as an ultraviolet absorption method, a Bradford method, a Lowry method, or a BCA method can also be used.
  • spectrophotometry methods may be influenced by other components contained in the sample, it is preferable to use an ELISA method using an antibody that specifically binds to ITGB1, PODXL or BCL7B.
  • the prognosis of a patient with pancreatic cancer is predicted from the staining score of the target protein or the amount of target protein by immunohistological staining using the pancreatic cancer tissue excised in the operation obtained in the above step.
  • samples obtained from pancreatic cancer patients and non-pancreatic cancer patients, as well as patients with various advanced pancreatic cancer patients, score score or target of target protein by immunohistological staining of ITGB1, PODXL and BCL7B contained in the sample under the same conditions Measure the amount of protein and accumulate data. The accumulated data and the measurement results are compared to determine the prognosis of a subject with pancreatic cancer.
  • the kit for prognostic diagnosing pancreatic cancer according to the present invention comprises an antibody against protein ITGB1 and an antibody against protein PODXL and / or an antibody against protein BCL7B.
  • the kit can be used in the above-mentioned method of the present invention using scoring of a target protein by immunohistological staining or ELISA. More specifically, for example, immunohistochemical staining is performed on the excised pancreatic cancer tissue with an anti-ITGB1 antibody and an anti-PODXL antibody and / or an anti-BCL7B antibody to score the expression level. By scoring, the expression level in one or more samples selected from the group consisting of ITGB1 and PODXL and BCL7B can be scored.
  • a sample obtained from a subject is added to a plate to which an anti-ITGB1 antibody and an anti-PODXL antibody and / or an anti-BCL7B antibody are bound, and washing is performed to differentiate ITGB1 and PODXL and / or BCL7B contained in the sample. Combine. Then, ITGB1 bound to the plate and PODXL and / or BCL7B are detected by a secondary antibody etc. bound to a labeling group, and consist of ITGB1 and PODXL and BCL7B, depending on the intensity of coloring according to the labeling group etc. The amount in one or more samples selected from the group can be measured.
  • the score of “2” Langerhans Island is comparable to that of “2” Langerhans Island, and is stronger than “3” Langerhans Island).
  • a score of 4 or more was determined as “high expression”, and a score of 3 or less was determined as “low expression”.
  • the results of the expression levels of 102 pancreatic cancer patients are shown in the following table.
  • an example of a pathological staining image of each protein is shown in FIGS. 2-2, 2-3, 3-2, 3-3, 4-2, 4-3, 5-2, and 5-3. 6-2, 6-3, 7-2, 7-3, 8-2, 8-3, 9-2, and 9-3.
  • Kaplan Meier shows the survival rate of all pancreatic cancer patients (Fig. 1). The period from surgery to final observation was 18 months to 192 months (median 64 months). Median survival for all 102 cases is 26 months (95% confidence interval, 23-33), 3 years survival rate is 35.1% (95% confidence interval, 25.6-44.8), 5 years survival rate Was 25.9% (95% confidence interval, 17.2-35.5).
  • Vav 3 (FIG. 2-1)
  • PODXL FIG. 3-1)
  • CCDC 88A FIG. 4-1
  • SCGB 1 D 2 FIG. 5-1)
  • BCL 7 B FIG.
  • pancreatic cancer cells are prognostic markers that can predict the prognosis of pancreatic cancer patients.
  • Table 12 shows the results of univariate analysis by the Cox proportional hazards regression model.
  • the odds ratio was in the range of 1.80 to 2.89.
  • the highest odds ratio was 2.56, which was stage III and stage IV.
  • Table 13 shows the results of multivariate analysis by the variable reduction method using the Cox proportional hazards regression model
  • Table 14 shows the results of multivariate analysis by the variable reduction method of the model.
  • Stages, PODXL, BCL7B, ITGB1, and ARHGEF4 were identified as hazards of the Cox proportional hazard model that can predict the prognosis of pancreatic cancer from the results of using two variable selection methods.
  • ⁇ Factor> -Stage a combination of stage 0 and stage I, a combination of stage III and stage IV-nerve invasion-PODXL, BCL7B, ITGB1, ARHGEF4 staining score-score of nerve invasion and each PODXL, BCL7B, ITGB1
  • the product of the staining scores of ARHGEF4 The combination of two proteins is all selected from four of PODXL, BCL7B, ITGB1 and ARHGEF4, and the product results of each staining score are shown in Table 15.
  • the prognostic marker can predict the prognosis of patients with pancreatic cancer with excellent sensitivity and specificity, in particular, patients with postoperative pancreatic cancer, by including ITGB1 and PODXL or a combination of ITGB1 and BCL7B.
  • the protein used for the above evaluation has the amino acid sequence of the following SEQ ID NO: Vav3; SEQ ID NO: 4 CCDC 88A; SEQ ID NO: 5 SCGB 1 D 2; SEQ ID NO: 6 ARHGEF 4; SEQ ID NO: 7 WASF 2; SEQ ID NO: 8
  • the prognostic marker according to the present invention makes it possible to predict "prognosis" of pancreatic cancer patients superior to staging in the clinical site, and therefore an appropriate treatment method for pancreatic cancer patients considering the prognosis of pancreatic cancer patients. It is possible to select

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Abstract

Le problème décrit par la présente invention est de fournir un marqueur de cancer présentant une sensibilité et une spécificité élevées et permettant de prédire le "pronostic" d'un patient atteint d'un cancer du pancréas. Un marqueur de pronostic du cancer du pancréas selon la présente invention contient une combinaison de protéine ITGB1 et de protéine PODXL et/ou de protéine BCL7B. La présente invention comprend : un kit de diagnostic du pronostic du cancer du pancréas, comprenant un anticorps dirigé contre la protéine ITGB1 et un anticorps dirigé contre la protéine PODXL et/ou un anticorps dirigé contre la protéine BCL7B; et un procédé de prédiction du pronostic du cancer du pancréas, comprenant la mesure du score d'immunohistochimie de la protéine ITGB1 et de la protéine PODXL et/ou de la protéine BCL7B dans un échantillon ou de la concentration de la protéine ITGB1 et de la protéine PODXL et/ou la protéine BCL7B dans l'échantillon.
PCT/JP2018/022186 2017-07-27 2018-06-11 Marqueur de pronostic du cancer du pancréas, kit de diagnostic du pronostic du cancer du pancréas et procédé de prédiction du pronostic du cancer du pancréas Ceased WO2019021654A1 (fr)

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Citations (4)

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Publication number Priority date Publication date Assignee Title
WO2016049045A1 (fr) * 2014-09-24 2016-03-31 Fred Hutchinson Cancer Research Center Diagnostic du cancer du pancréas
WO2017022472A1 (fr) * 2015-08-03 2017-02-09 国立大学法人名古屋大学 Marqueur pour des cellules souches mésenchymateuses non différenciées et leur utilisation
WO2017098915A1 (fr) * 2015-12-11 2017-06-15 国立大学法人高知大学 Marqueur du cancer du pancréas et des tumeurs intracanalaires papillaires et mucineuses
JP2017108686A (ja) * 2015-12-17 2017-06-22 国立大学法人北海道大学 膵癌の再発リスクの予測に用いるための診断薬及びキット、並びに予測方法

Patent Citations (4)

* Cited by examiner, † Cited by third party
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