Clinical Significance And Biological Behaviors Of IFIT2 Expression In Human Gastric Cancer

Objective The status of IFN signal pathway has been shown close association with the response of immune checkpoint blockade treatment against human advanced cancer.IFIT2,also known as interferon stimulated gene 54(ISG54),is one of the most highly responsive interferon-stimulated genes,involving in the inhibition of the proliferation and migration of cancer cells,and the regulation of viral replication,resulting in an anti-cancer as well as anti-viral effect.The present study aimed to investigate the clinical significance and biological function of the expression IFIT2 in human gastric cancer.Methods Immunohistochemistry assay was used to investigate the correlation between IFIT2 expression in cancer tissues and clinical parameters of the gastric cancer patients.Down-regulation of IFIT2 was performed by using RNAi method to investigate the role of IFIT2 in regulation of biological behaviors in human gastric cancer cell lines SGC-7901 and AGS.PCR and Western blot results indicated that the IFIT2 expression at the protein level and mRNA level was significantly decreased of SGC-7901 and AGS cells in the LV-IFIT2-shRNA group was significantly decreased compared with the LV-NC group.We performed CCK-8 assay,wound healing assay,transwell assay and cell cycle assay to examine the role of IFIT2 in cell viability,migration and cell cycle,respectively in human gastric cancer cell lines SGC-7901 and AGS.Results The immunohistochemistry assay showed that the IFIT2 expression in gastric cancer tissues was only correlated with the TNM stage of the patients(?~2=4.364,P=0.037),while it was not correlated with other clinical parameters,such as gender,age,tumor size,pathological stage,lymph node metastasis or distant metastasis.Patients with higher expression level of IFIT2 had prolonged OS than that with lower expression level,difference had statistical significance(?~2=10.990,P=0.001).The Cox regression model indicated that distant metastasis(HR=2.693.95%CI:1.164~6.232,P=0.021),IFIT2 high expression(HR=0.350,95%CI:0.169~0.727,P=0.005)were independent prognostic factors of gastric cancer.Decreased IFIT2 expression in human gastric cancer cell lines SGC-7901 and AGS significantly increased cell viability,cell migration and the ratios of cell in S phase.Conclusion Our present study demonstrated that the decreased IFIT2 expression was involved in the promotion of gastric cancer progression and predict poor outcome of the patients.Knockdown of IFIT2 expression in human gastric cancer cell lines significantly affected the cell viability,migration and cell cycle.