Polymorphism Rs2228226 With PT4a Gastric Adenocarcinoma Clinical Outcomes And Correlation Of The Involvement Of ARHGAP9 In Gastric Adenocarcinoma Cells

Background: We want to investigate whether GLI1 and ARHGAP9 common SNP rs2228226(G> C)is different from that clinical prognosis of the gastric adenocarcinoma patients.We want to preliminarily explore the effect of the expression of ARHGAP9 in gastric adenocarcinoma cells on biological behavior.We hope to reveal the mechanism of action of this SNP on gastric adenocarcinoma at the functional level of genes,in order to rs2228226 to become a new biological marker of gastric adenocarcinoma.Methods:(1)The research team used DHPLC and mass spectrometry to detect the pathological tissue DNA of 661 patients with p T4 a gastric adenocarcinoma after surgery.We design experiments based on statistics of rs2228226 polymorphisms and collection of corresponding clinical information of patients.In the following,we construct a Cox proportional hazard model to analyze the association between the rs2228226 polymorphism and the clinical prognosis of patients with p T4 a gastric adenocarcinoma and explore the stratification of chemotherapy.(2)We Construction of silenced ARHGAP9 si RNA to achieve up-regulation and down-regulation of ARHGAP9 expression levels in gastric adenocarcinoma cell lines based on q PCR technology to verify the expression level of ARHGAP9 in gastric adenocarcinoma cell lines.We used cell function experiments to verify the effects of ARHGAP9 on apoptosis,cell cycle,proliferation,migration,and invasion of gastric adenocarcinoma cells.Results:(1)We excluded patients who were diagnosed with distant metastasis,lost follow-up,and other non-compliance criteria according to the design of the project.This project finally selected 463 patients with complete data for analysis.The overall SNP classification was CC = 57,CG = 200,GG = 206.The total number of relapses and deaths were 323(69.8%)and 319(68.9%).Patients with CC genotype(MDFS = 12 months,MOS = 27 months)had a median progression-free survival and median overall survival that were significantly shorter than those with CG / GG genotypes(MDFS = 19 morths,Log-rank p = 0.003;MOS = 35 morths,Log-rank p =0.002).In the stratified study of patients receiving chemotherapy,CC genotype,advanced age,lymph node metastasis,moderate differentiation,and failure to achieve R0 resection were independent risk factors for recurrence(p <0.05).In addition,CC genotype,lymph node metastasis,and tumor recurrence were independent risk factors for death(p <0.05).(2)The q PCR results in this test showed that the expression of ARHGAP9 in gastric adenocarcinoma cell lines was significantly higher than that of normal gastric mucosal cell lines(p <0.05);Inhibition of ARHGAP9 expression could significantly reduce the proliferation,migration and invasion ability of gastric adenocarcinoma cells(p<0.05).Conclusions: The mutation homozygote(CC)is an independent risk factor that causes recurrence and death of patients with chemotherapy after p T4 a gastric adenocarcinoma in the rs2228226 polymorphism(G> C).It can be used as a potential marker to judge the prognosis of patients with chemotherapy after gastric adenocarcinoma.The expression of ARHGAP9 was increased in gastric adenocarcinoma cells,and inhibition of the expression of ARHGAP9 in gastric adenocarcinoma cells can inhibit its tumor biological behavior.