| Background: Gastric cancer is a highly heterogeneous malignancy with high morbidity and mortality.Early-onset gastric cancer is occult and most of the gastric cancer found is in advanced stage with a poor prognosis.In clinical work,the postoperative adjuvant chemotherapy for gastric cancer is mainly platinum-based chemotherapy regimens.It is found that gastric cancer with the same histopathological subtype has different efficacy when receiving the same chemotherapy regimen.Even today,the degree of malignancy and prognosis of gastric cancer still have been judged clinically by pathological type and differentiation.But in recent years,we can recognize the molecular mechanisms and related drug resistance mechanisms of gastric cancer evolution with the development of precision medicine,advances in the detection of genes and proteins,and the continuous in-depth research of the molecular biology of gastric cancer,which may provide theoretical mechanisms for individualized treatment of gastric cancer.There are many researches on molecular types of gastric cancer in the world,such as LEI,TCGA and ACRG studies.Compared with breast cancer,colorectal cancer,lung cancer,etc.,the molecular subtypes and individual treatment of gastric cancer in China still have been lagging behind.Therefore,it is of great significance to explore the molecular subtypes and prognosis of gastric cancer in China.ACRG proposed simple and reliable methods of operation,such as the detection of the relevant protein through immunohistochemical methods can also reflect the molecular types of gastric cancer.The research also provides markers for the molecular typing of gastric cancer whose study population are Asian with a certain reference significance to guide molecular subtyping of gastric cancer in China.Objective: To summarize Chinese clinicopathologic characters of gastric cancer patients;To explore the clinical features of different gastric cancer molecular subtyping and the corresponding survival prognosis;To analyze different molecular subtypes sensitivity for the chemotherapy drug(platinum-based)which provides a theoretical basis for the individualized treatment of postoperative adjuvant chemotherapy for gastric cancer.Method: Make a retrospective analysis on the cases who were diagnosed with stage I-IV gastric cancer and received radical surgery in Guangzhou First People's Hospital from 2005 to 2015 with complete information on clinica and survival prognosis data.Make a statistical analysis on clinical features,treatment programs,and prognosis of gastric cancer.Paraffin-embedded specimens of the cases that had sufficient samples were collected to make into tissue microarray and was stained by immunohistochemistry.To detect expression of MMR,E-cadherin and P21 by IHC method on tissue microarray.To adopt the method of stratification analysis to determine the gastric molecular subtypes based on protein expression in tumor tissue.To explore the molecular subtyping characteristics of gastric cancer in China.SPSS 22.0 software was used to analyze the clinical features,prognosis of different gastric cancer molecular subtypes and the prognosis of patients who recieve platinum-based adjuvant chemotherapy after surgery.Result: 1.159 cases were collected.The mean follow-up time of survival was 33.79 months,while median survival time was 26.0 months.2.The median age of onset of gastric cancer in Guangzhou First People's Hospital is 62 years old.Meanwhile,the incidence of gastric cancer in males was higher than females.More cases were found in the gastric antrum;In the Lauren classification,the rate of diffuse type was highest;When gastric cancer was found,it was mostly in stage III-IV,in fact mostly in advanced gastric cancer.3.The expression of MMR,E-cadherin and p21 protein was detected byimmunohistochemical staining.Among them,the deficiency of MMR expression was characterized by the loss of MLH1/PMS2 expression(21/159,13.2%)whose loss is more than that of MSH2/MSH6 expression(10/159,6.3%).The abnormal expression rate of E-cadherin was 34.6%(55/159).The high express-ion of p21 protein was 37.7%(60/159).The low expressio-n of p21 protein was 62.3%(99/159).4.By stratified analysis,gastric cancer can be divided into 4 molecular types: MMR-d,E-cadherin-a,p21-High,and p21-Low;after survival analysis of the four molecular types,it was found that survival prognosis of MMR-d subtype was the best,the p21-High subtype second,the prognosis of p21-Low subtype third,and the survival prognosis of E-cadherin-a subtype worst(p<0.0001).5.There were no significant correlations between different gastric cancer molecular types and clinicopathological factors including age,gender,tumor location,Lauren classification,TNM stage,differentiation,and neurovascular invasion.6.p21-high phenotype of gastric cancer is highly sensitive to platinum-based chemotherapy model,and its overall survival rate is significantly improved with platinum-based chemotherapy model.The survival rate of E-cadherin-a and p21-low with platinum-based was a little bit higher than that of non-platinum chemotherapy,but there was no significant difference between two cohort.There was no significant improvement in overall survival of MMR-d classification with platinum-based adjuvant chemotherapy.Conclusion: 1.Gastric cancers should be divided into the MMR-d,and E-cadherin-a,p21-Low and p21-High molecular subtypes.According to the clinical data of the four molecular subtypes and prognostic analysis,subtype of MMR-d prognosis was the best,e-cadherin-a the worst,and p21-High was higher than p21-Low.2.The above four molecular subtypes of gastric cancer have different sensitivity to platinum-based adjuvant chemotherapy.The subtype of p21-high was sensible for platinum-based adjuvant chemotherapy and overall survival rate of p21-high with platinum-based chemotherapy model is significantly improved. |
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