CN109975549A - Purposes of the tumour source IgG in diagnosis of pancreatic cancer or prognosis - Google Patents

Purposes of the tumour source IgG in diagnosis of pancreatic cancer or prognosis Download PDF

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CN109975549A
CN109975549A CN201910255462.0A CN201910255462A CN109975549A CN 109975549 A CN109975549 A CN 109975549A CN 201910255462 A CN201910255462 A CN 201910255462A CN 109975549 A CN109975549 A CN 109975549A
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cigg
quantitative reagent
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prognosis
antibody
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CN109975549B (en
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邱晓彦
赵玉沛
崔铭
廖泉
由磊
黄晶
刘乔飞
黄歆梅
张生华
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Peking University
Peking Union Medical College Hospital Chinese Academy of Medical Sciences
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    • 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
    • G01N33/6854—Immunoglobulins

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Abstract

This application involves purposes of the tumour source IgG in diagnosis of pancreatic cancer or prognosis.This application discloses the applications of the monoclonal antibody of a kind of specific recognition human tumour source immunoglobulin G (CIgG) heavy chain constant region, it is characterized by: dyeing pathological score judgement cancer of pancreas pathology differentiation degree and patient's prognosis using immunohistochemistry or immunofluorescence technique by antibody and being used to prepare a kind of immunohistochemical kit for detecting pancreas silver stain and assessing prognosis.The technical solution of the application provides foundation to improving in clinical and research work to the accuracy of cancer of pancreas prognosis evaluation with important application value for tumour individuation diagnosis and treatment project.

Description

Purposes of the tumour source IgG in diagnosis of pancreatic cancer or prognosis
Technical field
This application involves medical domains.In particular to clinical diagnosis, prognosis field.This application involves tumour sources Purposes of the IgG as pancreatic neoplasm prognostic marker.
Background technique
Cancer of pancreas is still one of highest malignant tumour of lethality at present.Pancreas cancer morbidity increases year by year, but its 5 years Survival rate still less than 10%, predict that cancer of pancreas will become in 10 years and occupy the deputy evil of tumour related mortality by pertinent literature Property tumour [1-2].Have multinomial clinicopathological parameters for assessing Patients with Pancreatic Cancer prognosis, including pathologic grading of cancer, lymph Tie [3-5] such as transfer case, CA19-9 levels；Some molecular markers, such as Ki-67, mTOR pathway molecule, hedgehog are logical Road molecule etc. is also applied to the Index for diagnosis of Patients with Pancreatic Cancer.However molecule prognosis accurate and effective for cancer of pancreas at present Marker is still very deficient [6-8].Therefore, accurate and effective cancer of pancreas prognostic marker is found, it has also become cancer of pancreas diagnosis and treatment The task of top priority.
Immunoglobulin (Ig) is a kind of classical immune molecule, is played a significant role in humoral immunity.Classics are immune Theory thinks that Ig is only capable of being generated by bone-marrow-derived lymphocyte.From 1996, multiple seminars such as Qiu Xiaoyan it is a series of research shows that Ig It can be generated by non-B cell, there are high-caliber expression especially in kinds of tumor cells.Tumour cell is generated as a result, Ig is defined as tumour source Ig (referred to as CIgG, Cancer IgG) [9-12].
Further investigation revealed that the antibody by specific recognition CIgG can detect in tumour cell or tissue CIgG's is specific expressed, using the antisense oligonucleotides and anti-Ig antibody of Ig specificity all can inhibit growth of tumour cell, Its apoptosis is induced, illustrates that tumour source Ig may play an important role [13-16] to the occurrence and development of malignant tumour.
Classified (2010 editions) according to WHO, originated from according to tissue, pancreatic neoplasm can be divided into: epithelial tumour, leaf are swollen Tumor, Germ-cell Tumors, secondary tumors；Wherein, epithelial tumour is divided into exocrine tumors and endocrine tumors.
Exocrine tumors are divided into:
Benign tumour: acinar cells cystadenoma, serous cystadenoma；
Precancerous lesion: 3 grades of tumour (PanIN-3) in pancreas epithelium, intraductal papillary mucinous tumors are with light-moderate Atypical hyperplasia, intraductal papillary mucinous tumors are with severe atypical hyperplasia, catheter channels shape Papillary Tumors, mucus Cystoma with mild-moderate atypical hyperplasia, mucinous cystic tumors with height atypical hyperplasia,
Malignant tumour: duct adenocarcinoma, adenosquamous carcinoma, mucinous carcinoma (the non-cystocarcinoma of mucus), hepatocyte-like cells, cephaloma, signet ring Cell cancer, undifferentiated carcinoma, undifferentiated carcinoma are with mamillary in osteoclastic sample giant cell, acinar cell carcinoma, acinar cells cystadenocarcinoma, conduit Mucinous neoplasms are with interstitial infiltration, mixed acinus-duct carcinoma, mixed acinus-endocrine cancer, interior point of mixed acinus- Secrete-duct carcinoma, Combination conduit-endocrine cancer, mucinous cystic tumors companion infiltrating cancer, pancreas blastoma, serosity capsule Gland cancer, Solid-pseudopapillary tumor；
Endocrine tumors are divided into:
The micro- adenoma of pancreas neuroendocrine；
Non-functional neuroendocrine tumors: NET, G1, NET, G2；
Neuroendocrine carcinoma NEC: cellule NEC, maxicell NEC；
Serotonin generative nature neuroendocrine tumors；
Gastrinoma；
Glucagonoma of pancreas；
Insulinoma；
Somatostatinoma；
Vasoactive intestinal peptide tumor.
Summary of the invention
According to some embodiments of the application, CIgG is provided as pancreatic neoplasm diagnosis and/or prognostic markers object Purposes.
According to some embodiments of the application, the quantitative reagent for providing CIgG is preparing the purposes in medical instrument.
In some embodiments, the diagnosis and/or prognosis of pancreatic neoplasm are used for according to the medical instrument of the application.
In a specific embodiment, the diagnosis of pancreatic neoplasm is used for according to the medical instrument of the application.
In another specific embodiment, the prognosis of pancreatic neoplasm is used for according to the medical instrument of the application.
In some embodiments, the quantitative reagent of CIgG identifies and combines people CIgG.Therefore, the quantitative reagent energy of CIgG Enough determine CIgG content (concentration) in the sample or expression.The sample is originated from subject.
In some embodiments, the quantitative reagent of CIgG is the quantitative reagent of CIgG heavy chain or CIgG light chain.
In some embodiments, the quantitative reagent of the CIgG is the quantitative reagent of CIgG heavy chain constant region.
In some embodiments, the quantitative reagent of the CIgG is the quantitative reagent of CIgG constant region of light chain.
In some embodiments, the quantitative reagent of CIgG identifies and combines one in following epitope or combination: VL、CL、VH、CH1、CH2、CH3。
In specific embodiments, the quantitative reagent of CIgG identifies and combines one in following epitope or group It closes: CL, CH1.
In specific embodiments, the quantitative reagent of CIgG identifies and combines CL.
In specific embodiments, the quantitative reagent of CIgG identifies and combines CH1.
In some embodiments, quantitative reagent determines the protein level of CIgG.
In some embodiments, the quantitative reagent is selected from: antibody or its antigen-binding fragment, Mass Spectrometric Identification reagent.
In some embodiments, following form: diagnosticum, kit, core is presented as according to the medical instrument of the application Piece, test paper, microwell plate (such as 48,96 holes).
In some embodiments, epithelial pancreatic neoplasm is suitable for according to the medical instrument of the application.
In some embodiments, epithelial pancreatic neoplasm is selected from the following a kind of or combination: exocrine pancreas tumour, interior Secrete pancreatic neoplasm.
In some embodiments, selected from the following a kind of or combination: conduit is suitable for according to the medical instrument of the application Gland cancer, adenosquamous carcinoma, mucinous carcinoma, hepatocyte-like cells, cephaloma, signet ring cell cancer, undifferentiated carcinoma, undifferentiated carcinoma are big and small with osteoclastic sample Born of the same parents, acinar cell carcinoma, acinar cells cystadenocarcinoma, intraductal papillary mucinous tumors are infiltrated with interstitial, mixed acinus-is led Pipe cancer, mixed acinus-endocrine cancer, mixed acinus-endocrine-duct carcinoma, Combination conduit-endocrine cancer, mucus Cystoma is with infiltrating cancer, pancreas blastoma, serous cystadenocarcinoma, Solid-pseudopapillary tumor.
In specific embodiments, the quantitative reagent of CIgG is provided in preparing duct adenocarcinoma diagnosis/prognostic agent Purposes.
In some embodiments, prognosis refers to selected from the following a kind of or combination: the final result of prognosis subject, prognosis by The existence of the therapeutic effect, prognosis subject of examination person.
In some embodiments, compared to control, the expression of CIgG is high, and instruction subject has worse pre- Afterwards, such as shorter existence.
In some specific embodiments, existence include but is not limited to overall survival, without tumor existence, it is annual deposit, two Year existence, five Nian Shengcun.
In some specific embodiments, the expression height of CIgG refers to: immunohistochemistry or immunofluorescence dyeing are strong Degree high (such as, but not limited to using H points-scoring system), the cell proportion height of stained positive or combination.
In some specific embodiments, the technical solution of the application is particularly suitable for the trouble of the pancreatic neoplasm through treating Person.In some specific embodiments, the pancreatic neoplasm that the technical solution of the application is suitable for treating through surgical discectomy is suffered from Person.
It in some embodiments, can be using the compound that any and CIgG is combined as quantitative reagent or can Determine the reagent (such as MS Mass Spectrometric Identification) of CIgG level.
In some specific embodiments, the quantitative reagent of CIgG is polyclonal antibody or monoclonal antibody.
In some specific embodiments, polyclonal antibody or monoclonal antibody are not limited to secreted by specific cells strain.
In some specific embodiments, antibody be originated from any species, such as mouse, rabbit, horse, fowl, sheep, Camelidae, dog, Ox, primate；Either recombinant antibodies, chimeric antibody.
Technical staff knows that antibody realizes the function to antigen binding, may not use its complete form, be also possible to antigen Binding fragment.Thus, in some embodiments, antigen-binding fragment can be Fab, Fv, scFv, Fab ', F (ab ') 2.
According to some embodiments of the application, the two combination of CIgG expression and N by stages is provided as pancreas The purposes of diagnosing tumor and/or prognostic markers object.
In some embodiments, CIgG expression and N are by stages (N1, N0) that the independent of ductal adenocarcinoma of pancreas prognosis is endangered Dangerous factor.
In the context of this application, in following sample determine CIgG expression: blood (whole blood, blood plasma, Serum), saliva, cerebrospinal fluid, ascites, tissue biopsy, alimentary canal liquid, urine, excreta, tumor tissues.
In specific embodiments, the sample is tumor tissues or blood (whole blood, blood plasma, serum).
Detailed description of the invention
Expression water of Figure 1A to Fig. 1 D:CIgG level in training set and verifying two groups of ductal adenocarcinoma of pancreas tumor tissues of collection Averagely it is significantly higher than cancer beside organism, P < 0.001.
Fig. 2A and Fig. 2 B: antibody test CIgG high level expression indicates ductal adenocarcinoma of pancreas patient poor prognosis.
Fig. 3 A and Fig. 3 B: detecting the express spectra of CIgG in patient and normal human serum, and arrow shows the band of CIgG.
Specific embodiment
Term
" antigen-binding fragment " described herein refers to Fab segment, Fab ' segment, F with antigen-binding activity (ab ') 2 segment and Fv segment.
The term " antigen binding site " of the application refer to it is discontinuous on antigen, by the application antibody or antigen-binding fragment The three-dimensional space site of identification.
Term " epitope " refers to the site on antigen in conjunction with immunoglobulin or antibody specificity.Epitope can be by adjacent Amino acid or non-conterminous amino acid arranged side by side folded by the three-level of protein formed.It is formed by adjacent amino acid Epitope usually kept after being exposed to denaturing solvent, and folded by three-level the epitope to be formed usually denaturing solvent processing after It loses.Epitope includes usually at least 3-15 amino acid with unique space conformation.Determine any epitope by given antibody knot The method of conjunction is well known in the art, including immunoblotting and immunoprecipitation test and analyze etc..Determine the space structure of epitope The method of elephant includes technology and the techniques described herein in this field, such as x-ray crystal analysis method and two dimensional NMR Deng.
Embodiment
Following tests is audited by Ethics Committee, Chinese Academy of Medical Sciences Beijing Union Medical College Hospital, and is abided by Helsinki and declared Speech, all patients are informed the purpose of sample collection and storage in detail and sign written consent form.
1. case and experimental design
326 pathological examinations through radical surgery excision are included in be diagnosed as by ductal adenocarcinoma of pancreas patient tumors and cancer Tissue specimen.Pathological diagnosis and staging scale refer to American Cancer Society's Cancer Staging Handbook the 7th edition.
Exclusion criteria include: it is preoperative receive chemicotherapy, perioperative mortality, receive it is unknown in addition to gemcitabine and S1 Chemotherapy regimen, Follow-up Data missing.It is matched by age and gender, 326 case stratified randoms are grouped into training set and verifying Collection includes 163 cases.The median follow-up time time of training set is 17 months, and the median follow-up time time for verifying collection is 18 months.
2. prepared by organization chip
Model machine (Beecher instrument company, the U.S.) is put manually by organization chip by paraffin embedding by pancreatic tumour and cancer Tissue samples are prepared as organization chip, every spot diameter 1.5mm.
3. immunohistochemical staining
Anti- CIgG monoclonal antibody can voluntarily be prepared with laboratory or commercially be obtained, and immunohistochemistry secondary antibody is public purchased from DAKO Department.
Immunohistochemical staining step:
Paraffin section, which is placed in dimethylbenzene, to be impregnated 20 minutes, is renewed fresh dimethylbenzene and is repeated once；
Histotomy after dewaxing is impregnated 5 minutes 2 times in 100% ethyl alcohol, 95% ethyl alcohol, 80% ethyl alcohol, distilled water It is each to impregnate 5 minutes；
Antigen retrieval buffers are 9.0 buffer of Tris-EDTA pH, and antigen retrieval buffers are heated to boiling with pressure cooker, will Slice is put into, and is heated to timing 2 minutes, cooled to room temperature after steaming；
3% hydrogen peroxide (H of fresh configuration2O2), piece is dripped, is protected from light incubation 10 minutes at room temperature；
It is closed 20 minutes with normal sheep serum working solution room temperature；
Anti- CIgG monoclonal antibody (5 μ g/ml) is prepared with phosphate buffer (PBS), and 37 DEG C are incubated for 1h with slice；PBS It washes 3 times, every time 5 minutes；
It uses DAKO secondary antibody colour reagent (EnVision Detection Kit), room temperature is reacted 25 minutes with histotomy, PBS is washed 5 minutes × 3 times；
- DAB colour developing, drips piece, microscopic observation reaction result；
Haematoxylin redyeing nucleus 1 minute, tap water oil blackeite 5 minutes；
The dehydration of ethyl alcohol uplink: 80% ethyl alcohol 5 minutes, 95% ethyl alcohol 5 minutes, 100% ethyl alcohol 5 minutes, 100% ethyl alcohol 5 divide Clock；Neutral gum mounting.
Slice is subjected to digitlization panoramic scanning by company, Hungary Panoramic MIDI scanner.
4. ImmunohistochemistryResults Results interpretation
Immunohistochemistry scoring is based on H points-scoring system, that is, passes through staining power rank (0,1,2,3) and positive cell ratio (0-100) multiplication obtains score [17].Immunohistochemistry scores by two researcher's independently interpretations, is finally averaged.Base In training set data, by X-tile 3.6.1 software [18], show that antibody dyeing scoring cutoff value is 148 points.It scores small It is determined as tumour source IgG low expression group in being equal to 148 points, tumour source IgG high expression group is determined as higher than 148 points.
Immunohistochemical staining is carried out to the clinical samples that an example is diagnosed as undifferentiated carcinoma, display staining power rank is 0 (figure As not showing).
5. statistical analysis
Using statistics software SPSS 24.0, GraphPad Prism 6, statistical significant difference be defined as P < 0.05.Overall survival, which is defined as operation, to be terminated to death or follow-up to end.Enumeration data application Chi-square Test, measurement data It is examined using t, to evaluate tumour source IgG expression with each variable of cancer of pancreas case clinical pathology with the presence or absence of correlation. Using the difference of Wilcoxon signed rank test comparison of tumor source IgG expression in pancreatic tumour tissue and cancer beside organism It is different.Analysis of Survival Time is carried out using Kaplan-Meier curve and is compared by log-rank inspection.Using Cox ratio Risk regression model carries out single factor test and multifactor survival analysis.
6. with the CIgG in anti-CIgG antibody test ductal adenocarcinoma of pancreas patient and normal healthy controls serum.In clinical samples CIgG express spectra is different from normal healthy controls (Fig. 3 A and Fig. 3 B).
7. experimental result
7.1 expression by anti-CIgG antibody test CIgG in ductal adenocarcinoma of pancreas tumour and cancer beside organism
According to standards of grading, expression of the CIgG in training set and verifying two groups of ductal adenocarcinoma of pancreas tumor tissues of collection It is all remarkably higher than cancer beside organism, P < 0.001 (Figure 1A, Fig. 1 C and Figure 1B, Fig. 1 D).Prompt CIgG expression to pancreatic duct gland Cancer has good additive diagnostic value.
The relationship of 7.2 anti-CIgG antibody test CIgG expressions and ductal adenocarcinoma of pancreas patient clinical pathological characters
Result of study shows that CIgG expression is significant related to ductal adenocarcinoma of pancreas tumor differentiation degree, leads with pancreas Pipe adenocarcinoma patients' age, gender, Smoking And Drinking history, tumor locus, T by stages, N by stages, the uncorrelated (table of postoperative adjuvant therapy situation 1)。
The correlation of table 1.CIgG expression and clinical pathologic characteristic
7.3 anti-CIgG antibody test CIgG expressions are for assessing ductal adenocarcinoma of pancreas patient's prognosis
According to standards of grading, we are by Kaplan-Meier survival analysis respectively in training set and verifying collection pancreatic duct CIgG scoring high level group is compared with the prognosis situation of low-level group in adenocarcinoma patients.
The results show that CIgG scores, it is low to be substantially less than CIgG scoring for the survival rate of the ductal adenocarcinoma of pancreas patient of high level group Horizontal group (training set: P < 0.001, verifying collection: P=0.001), illustrates that the high level expression indication ductal adenocarcinoma of pancreas of CIgG is suffered from Person's poor prognosis (Fig. 2A and Fig. 2 B).
The regression analysis that 7.4 each indexs influence ductal adenocarcinoma of pancreas patients overall survival's phase
Overall survival correlation point is carried out to training set and verifying collection ductal adenocarcinoma of pancreas patient using Cox regression analysis Analysis.Single-factor regressioning analysis discovery: in training set, (P=0.004) and CIgG are commented by stages by tumor differentiation degree (P < 0.001), N Divide (P < 0.001) related to ductal adenocarcinoma of pancreas patients overall survival's phase；Verifying is concentrated, N (P=0.023) and CIgG scoring by stages (P=0.002) related to ductal adenocarcinoma of pancreas patients overall survival's phase.Multinomial logistic regression discovery: CIgG scoring (training set: P < 0.001, verifying collection: P=0.004) (training set: P=0.017, verifying collect: P=0.077) being to influence pancreatic duct by stages with N The independent hazard factor (table 2) of adenocarcinoma patients' prognosis.
Table 2.Cox Regression Analysis Result
In conclusion CIgG is significantly high to be expressed in ductal adenocarcinoma of pancreas tumor tissues, CIgG scoring high level indication pancreas Duct adenocarcinoma patient's poor prognosis, CIgG scoring are the independent hazard factors of ductal adenocarcinoma of pancreas patient's prognosis.CIgG monoclonal antibody can Reference index as cancer of pancreas Index for diagnosis is with helping directive clinical diagnosis and treatment.
Bibliography
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Claims (10)

  1. The quantitative reagent of 1.CIgG is preparing the purposes in medical instrument, in which:
    The medical instrument is used for the diagnosis and/or prognosis of pancreatic neoplasm, preferably prognosis；
    The quantitative reagent of the CIgG can determine the content or expression of CIgG；
    It is preferred that the quantitative reagent of the CIgG is the quantitative reagent of CIgG heavy chain or CIgG light chain；
    It is preferred that the quantitative reagent of the CIgG is the quantitative reagent of CIgG heavy chain constant region or CIgG constant region of light chain；
    It is preferred that the quantitative reagent of the CIgG is the quantitative reagent selected from following epitope: VL, CL, VH, CH1, CH2, CH3 or A combination thereof；It is further preferred that CL, CH1, or combinations thereof；
    The quantitative reagent refers to quantifying in protein level；
    It is preferred that the quantitative reagent is selected from: antibody or its antigen-binding fragment, Mass Spectrometric Identification reagent；
    It is preferred that the medical instrument is selected from the following a kind of or combines: diagnosticum, kit, chip, test paper, orifice plate；
    The protein level is CIgG in the protein level in following sample: blood, whole blood, blood plasma, serum, saliva, brain Spinal fluid, ascites, tissue biopsy, alimentary canal liquid, urine, excreta, tumor tissues.
  2. 2. purposes according to claim 1, the pancreatic neoplasm is epithelial pancreatic neoplasm；
    It is preferred that epithelial pancreatic neoplasm is selected from the following a kind of or combines: exocrine pancreas tumour, endocrine pancreas tumour；
    It is further preferred that exocrine pancreas tumour is selected from the following a kind of or combines: duct adenocarcinoma, adenosquamous carcinoma, mucinous carcinoma, liver sample gland Cancer, cephaloma, signet ring cell cancer, undifferentiated carcinoma, undifferentiated carcinoma are with osteoclastic sample giant cell, acinar cell carcinoma, acinar cells capsule gland Cancer, intraductal papillary mucinous tumors with interstitial infiltration, mixed acinus-duct carcinoma, mixed acinus-endocrine cancer, Mixed acinus-endocrine-duct carcinoma, Combination conduit-endocrine cancer, mucinous cystic tumors are female with infiltrating cancer, pancreas Cytoma, serous cystadenocarcinoma, Solid-pseudopapillary tumor；
    Most preferably, the pancreatic neoplasm is ductal adenocarcinoma of pancreas.
  3. 3. purposes according to claim 1, the prognosis refers to selected from the following a kind of or combination: the knot of prognosis subject The existence of office, the therapeutic effect of prognosis subject, prognosis subject；
    It is preferred that the expression of CIgG is high, instruction subject has worse prognosis.
  4. 4. purposes according to claim 3, in which:
    The subject is pancreatic neoplasm patient；
    It is preferred that the subject is the pancreatic neoplasm patient through treating；
    The treatment is surgical discectomy.
  5. 5. purposes according to claim 3, wherein the existence is selected from: overall survival, without tumor existence, it is annual deposit, two Year existence, five Nian Shengcun.
  6. 6. purposes according to claim 1, in which:
    The antibody is polyclonal antibody or monoclonal antibody；
    The antibody is originated from: mouse, rabbit, horse, fowl, sheep, Camelidae, dog, ox, primate, recombinant antibodies；
    The antigen-binding fragment is selected from: Fab, Fv, scFv, Fab ', F (ab ') 2.
  7. The combination of the quantitative reagent and N of 7.CIgG by stages is preparing the purposes in medical instrument, in which:
    The medical instrument is used for the prognosis of pancreatic neoplasm；
    The quantitative reagent of the CIgG can determine the content or expression of CIgG；
    It is preferred that the quantitative reagent of the CIgG is the quantitative reagent of CIgG heavy chain or CIgG light chain；
    It is preferred that the quantitative reagent of the CIgG is the quantitative reagent of CIgG heavy chain constant region or CIgG constant region of light chain；
    It is preferred that the quantitative reagent of the CIgG is the quantitative reagent selected from following epitope: VL, CL, VH, CH1, CH2, CH3 or A combination thereof；It is further preferred that CL, CH1, or combinations thereof；
    The quantitative reagent refers to quantifying in protein level；
    It is preferred that the quantitative reagent is selected from: antibody or its antigen-binding fragment, Mass Spectrometric Identification reagent；
    The medical instrument is selected from the following a kind of or combines: diagnosticum, kit, chip, test paper, orifice plate；
    The protein level is CIgG in the protein level in following sample: blood, whole blood, blood plasma, serum, saliva, brain Spinal fluid, ascites, tissue biopsy, alimentary canal liquid, urine, excreta, tumor tissues.
  8. 8. purposes according to claim 7, the pancreatic neoplasm is duct adenocarcinoma；
    The prognosis refers to selected from the following a kind of or combination: the final result of prognosis subject, the therapeutic effect of prognosis subject, pre- The existence of subject afterwards；
    It is preferred that it is described existence be selected from: overall survival, without tumor existence, it is annual deposit, it is biennial deposit, five Nian Shengcun；
    The subject is pancreatic neoplasm patient, preferably the pancreatic neoplasm patient through treating, more preferably through the pancreas of surgical discectomy Gland tumor patient.
  9. 9. purposes according to claim 7, in which:
    The antibody is polyclonal antibody or monoclonal antibody；
    The antibody is originated from: mouse, rabbit, horse, fowl, sheep, Camelidae, dog, ox, primate, recombinant antibodies；
    The antigen-binding fragment is selected from: Fab, Fv, scFv, Fab ', F (ab ') 2.
  10. Purposes of the quantitative reagent of 10.CIgG in the medical instrument for preparing Diagnosis of Pancreatic duct adenocarcinoma, in which:
    The quantitative reagent of the CIgG can determine CIgG content in blood or expression；The quantitative reagent refers to Protein level quantifies；
    It is preferred that the quantitative reagent of the CIgG is the quantitative reagent of CIgG heavy chain or CIgG light chain；It is preferred that the CIgG's quantifies Reagent is the quantitative reagent of CIgG heavy chain constant region or CIgG constant region of light chain；
    It is preferred that the quantitative reagent of the CIgG is the quantitative reagent selected from following epitope: VL, CL, VH, CH1, CH2, CH3 or A combination thereof；It is further preferred that CL, CH1, or combinations thereof；
    It is preferred that the quantitative reagent is selected from: antibody or its antigen-binding fragment, Mass Spectrometric Identification reagent；
    The antibody is polyclonal antibody or monoclonal antibody；The antibody is originated from: mouse, rabbit, horse, fowl, sheep, Camelidae, dog, Ox, primate, recombinant antibodies；
    The antigen-binding fragment is selected from: Fab, Fv, scFv, Fab ', F (ab ') 2；
    It is preferred that the medical instrument is selected from the following a kind of or combines: diagnosticum, kit, chip, test paper, orifice plate.
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CN111208304A (en) * 2020-01-20 2020-05-29 中国医学科学院北京协和医院 Use of tumor-derived IgG in diagnosis and prognosis of parathyroid cancer
CN113257370A (en) * 2021-05-12 2021-08-13 中国医学科学院北京协和医院 PNET recurrence risk prediction model based on clinical pathology basic information and VISTA detection
CN114235805A (en) * 2021-12-16 2022-03-25 中国医学科学院北京协和医院 System for prognosis evaluation of pancreatic solid pseudopapilloma
CN115212308A (en) * 2021-04-15 2022-10-21 中国医学科学院基础医学研究所 Use of targeting agents for the GASDERMIN E pathway in the treatment of pancreatic cancer

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Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111208304A (en) * 2020-01-20 2020-05-29 中国医学科学院北京协和医院 Use of tumor-derived IgG in diagnosis and prognosis of parathyroid cancer
CN115212308A (en) * 2021-04-15 2022-10-21 中国医学科学院基础医学研究所 Use of targeting agents for the GASDERMIN E pathway in the treatment of pancreatic cancer
CN115212308B (en) * 2021-04-15 2023-10-20 中国医学科学院基础医学研究所 Application of GASDERMIN E pathway targeting agent in treating pancreatic cancer
CN113257370A (en) * 2021-05-12 2021-08-13 中国医学科学院北京协和医院 PNET recurrence risk prediction model based on clinical pathology basic information and VISTA detection
CN113257370B (en) * 2021-05-12 2022-09-02 中国医学科学院北京协和医院 PNET recurrence risk prediction model based on clinical pathology basic information and VISTA detection
CN114235805A (en) * 2021-12-16 2022-03-25 中国医学科学院北京协和医院 System for prognosis evaluation of pancreatic solid pseudopapilloma

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