The Correlation Between Molecular Clsssification And Prognosis Of Gastric Adenocarcinoma

Objective: Gastric cancer is a highly heterogeneous tumor with epidemiological and histopathological differences,and its tumorigenesis is the result of a multifactorial long-term process.However,the treatment of gastric cancer is uniform regardless of the pathology type.With the development of next generation sequencing,and the biological detection technologies,the continuous update of molecular targeted therapy and the arrival of the era of precision treatment,the understanding of gastric cancer in molecular and genetic respect have been more deep.Previous general classification and microscopic pathological subtype can not provide sufficient basis for individual treatment.Therefore,a large number of researchers have explored the molecular classification of gastric cancer.The five kind of molecular classification published in 2016 is the summary of previous studies.This research detects the prognostic and survival-related indicators reported in previous reseaches,and divides the patients into five subtypes by immunohistochemistry and fluorescence situ hybridization.Based on the five kind of molecular calssification,our study sorted the patients through the molecular markers,analyzed the correlation between different subtype and moleculars,and compared the prognosis of different molecular classification,in order to find probable prognostic predictors.Contents and Methods: We collected the patients of gastric adenocarcinoma who had accepted the gastrectomy at Zhengzhou University Affiliated Cancer Hospital from December 2013 to January 2017.The patients were followed up by medical history or telephone.We screening patients who were able to follow-up the disease-free survival(DFS)into groups.Immunohistochemistry method was used to detect moluculars of patient postoperative tumor tissue,including Her-2,PD-L1,MLH1,PMS2,MSH2,MSH6,E-cadherin,p53,MUC5 AC,MUC6,MUC2,CD10,CDX-2.The classification was performed according to the expression level of MMR,p53,and E-cadherin.Chi-square test was used to analyze the correlation between each molecular and classifications.Kaplan-Meir survival analysis was used to compare the DFS of different classifications and expression level of each molecular.The patients and tumor basic characteristics and immunohistochemistry indicators were enrolled into the COX risk proportional regression model for multivariate analysis.P < 0.05 was considered to have statistical significane.Results: According to medical records and telephone follow-up,a total of 138 patients were attained DFS,107 of which met the enrollment criterias.There were 82 males(76.6%),and 25 females(23.4%).The median age was 54 years.There were 91 patients(85%)with pathological TNM III,and 13 patients(12.1%)with pathological TNM II and 3 patients(2.8%)with pathological TNM I.1.The molecular indactors of Her-2 protein expression 0: 68(63.60%),1+: 16(15%),2+: 16(15%),3+: 7(6.5%);PD-L1 expression <1%: 89(83.2%),1%-5%: 8(7.5%),>5%: 10(9.3%);MMR deficiency(MSI-H): 17(15.9%),perfection(MSS): 90(84.1%);E-cadherin positive: 98(91.6%),negative: 9(8.4%);p53 mutation: 63(58.9%),wild: 44(41.1%);MUC5AC positive: 64(59.8%),negative: 43(40.2%);MUC6 positive: 50(46.7%),negative: 57(53.3%);MUC2 positive: 41(38.3%),negative: 66(61.7%);CD10 positive: 28(26.2%),negative: 79(73.8%);CDX-2 positive: 67(62.6%),negative: 40(37.4%).2.According to the results of immunohistochemistry,the molecular classification were: E-cadherin positive + p53 mutant + MSS: 49 patients(45.8%);E-cadherin positive + p53 wild + MSS: 34(31.8%);E-cadherin positive + p53 mutant + MSI-H: 10(9.3%);E-cadherin positive + p53 wild + MSI-H: 5(4.7%);E-cadherin negative + p53 wild + MSI-H:2(1.9%);E-cadherin negative + p53 mutant + MSS: 4(3.7%);E-cadherin negative + p53 wild + MSS: 3(2.8%).There was no significant statistically difference of DFS between the subtypes(P=0.841).3.There have significant statistical differences of CDX-2 expression status: positive vs negative m DFS=19.6 months vs 15.1 months(Log Rank P=0.027).The statistical differences of m DFS and other molecular indicators have not observed.4.MMR protein level was correlated with MUC5 AC and Her-2 expression.The positive expression of MUC5 AC increased in MMR deficiency(MSI-H),and negative expression increased in perfection(MSS)patients(P=0.014),Her-2 protein positive expression was reduced in MSI-H patient(P=0.033).5.The COX risk proportional regression model presented that patients with CDX-2 positive expression(P=0.004 HR:0.39 95% CI:0.204-0.746),MUC5 AC negative expression(P=0.032 HR:1.779 95% CI:1.053-3.006),Her-2 protein amplification had a good prognosis(P=0.008),and patients with N3 had the worst prognosis(P=0.027).Conclusion: This reaearch based on five kind of molecular classification detecting 13 molecular indicators to classified the enrolled gastric adenocarcionoma patients.Otherwise,the correlation of prognosis and molecular subtypes and indicators was analysed.1.There is no statistical difference between m DFS and different classifications;2.Gastric adenocarcinoma patients with MSI-H have a higher negative expression rate of MUC5 AC and a lower positive rate of Her-2 protein;3.Patients of gastric adenocarcinoma have good prognosis with CDX-2 positive expression,MUC5 AC negative expression,and Her-2 protein amplification;4.The expression of CDX-2,MUC5 AC and MMR can be further analyzed as prognostic factors of gastric adenocarcinoma.