GRB7 To Promote The Progression Of Gastric Cancer

Background:Gastric cancer is a clinically common tumor,showing an upward trend of both incidence and mortality.GRB7 has been identified as a vital regulator in tumor progression.This study aims to uncover the biological function of GRB7 in gastric cancer process.Methods:Based on the Timer、Kaplan-Meier Plotter and TCGA database,differentially analyze the expression levels of GRB7 in cancer tissues and non-cancer tissues of different tumors;The Timer databases and CIBERSORT algorithm were used to analyze the correlation between the expression of GRB7 and immune cells.The correlation between GRB7 and m6 A methylation was also explored.The biological function of GRB7 in the development and progression of GC was determined by gene set enrichment analysis;Differential levels of GRB7 in gastric cancer tissues and cell lines were detected by immunohisto-chemical(IHC)staining using a tissue microarray(TMA),quantitative reverse transcription PCR(q RT-PCR)and Western blotting,respectively.The prognostic value of GRB7 in gastric cancer was assessed by Kaplan Meier analyses.Furthermore,gastric cancer cell lines AGS and MGC-803 were transfected with short hairpin RNAs against GRB7.The biological function of GRB7 in gastric cancer cells were examined by CCK-8,Transwell assay and flow cytometry.Results:GRB7 was up-regulated in gastric cancer tissues and cell lines,and its express-ion was associated with overall survival of gastric cancer patients.The results of immune infiltration analysis indicated that GC tissues with high expression levels of GRB7 usually contained a higher proportion of macrophages M0 and NK cells resting.GRB7 expression level in GC was significantly correlated with macrophage M0(R=0.34,P=4.3E-07)and NK cells resting(R=0.2,P=0.004);Moreover,GRB7 knockdown decreased proliferative,migratory abilities,as well as promoted cell apoptosis in gastric cancer cells.Further study suggested that GRB7 silencing could suppress gastric cancer tumor growth in vivo.Conclusions:The expression of GRB7 was significantly higher in gastric cancer tissues relative to normal paracancerous tissues,and the higher the expression of GRB7,the worse the prognosis of gastric cancer patients;high GRB7 expression was associated with the immune microenvironment of gastric cancer;patients in the low GRB7 expression group showed better efficacy when receiving immunotherapy;inhibition of GRB7 expression reduced the proliferation and inhibited the migration of gastric cancer cells,and increased the apoptosis of gastric cancer cells.