High KRT8 Expression Promotes Metastasisand Influences Prognosis Of Gastric Cancer

Objective: To detected the expression of KRT8 in human gastric cancer tissues and adjacent non-cancerous tissues and 5 human gastric cancer cell lines(BGC-823?SGC-7901?MGC-803?HGC-27?AGS),investigate its role in the biological behavior of gastric cancer cells.Methods: 1.Predicted KRT8 m RNA expression in gastric cancer by public cancer dataset,detected the expression of KRT8 m RNA in 50 cases of gastric cancer tissues and their matching adjacent non-cancerous tissues by qRT-PCR.2.Detected the expression of KRT8 m RNA in 70 cases of gastric cancer tissues and their matching adjacent non-cancerous tissues by immunohistochemistry,and analyzed the relationship between KRT8 expression and clinicopathological factors.3.Upregulated or downregulated expression of KRT8,the ability of migration was determined by transwell assay.4.To determined the difference of EMT related protein and TGF?/smad pathway related protein in gastric cancer cells by western blot.Results: 1.qRT-PCR result showed that the expression of KRT8 in normal tissues was upregulated(68%,34/50),compared with adjacent non-cancerous tissues.2.As compared to the GC with low-KRT8 expression,the GC with high-KRT8 expression can be a more tumor invasion depth(p=0.002)and more advanced clinical stage(p=0.025).3.The Kaplan-Meier analyses result demonstrated that higher KRT8 m RNA expression is correlated with the poor overall survival(OS),as well as progression-free(FP)survival of GC patients,Cox regression analysis demonstrated that KRT8 expression level and clinical stage were independent prognostic indicators for the overall survival of patients with gastric cancer.4.The expression level of KRT8 in HGC-27 cells was highest and in AGS cells was lowest.KRT8 expression was correlation with EMT and migration.5.KRT8 promotes gastric cancer migration and EMT by regulated TGF?/smad pathway.Conclusions: The results indicate that KRT8 plays important role in gastric carcinogenesis and progression and may promote gastric cancer metastasis by inducing EMT.KRT8 will be a new diagnostic marker and therapeutic target in gastric cancer.