The roles of E2Fs in gastric cancer: the transcription factors E2F1/2/3/4/5 as potential therapeutic targets and E2F6/7/8 as new prognostic biomarkers in gastric cancer
Abstract Background E2F is a family of transcription factor proteins with multiple functions; E2F proteins are involved in cell cycle regulation, cell differentiation, the DNA damage response and cell death. Studies have shown that E2Fs have prognostic significance in many cancers, but the expression patterns and prognostic values of E2Fs in gastric cancer have not been systematically elucidated. Methods In this study, we used the ONCOMINE database and UALCAN online analysis website to compare the transcriptional levels and expression of eight E2F family members between gastric cancer and normal samples. UALCAN was also used to analyze the relationship between the expression of 8 E2F members and clinicopathological parameters. The prognostic value of the E2Fs were determined by Kaplan-Meier Plotter. A protein-protein interaction (PPI) network was constructed using the STRING database. The functions and pathways of E2F family and its neighboring 50 frequently changed genes were analyzed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) software. Finally, quantitative PCR was used to verify the expression of E2Fs in gastric cancer cells. Results The expression patterns of 8 E2F members were significantly related to the clinical cancer stage and tumor grade of gastric cancer patients. High mRNA expression of E2F1/2/3/4/5 was a prognostic factor for poor OS in gastric cancer patients, while high expression of E2F6/7/8 was associated with better OS. In addition, a high mutation rate (46%) for E2Fs was observed in patients with gastric cancer. The expression levels of E2F1/2/3/5/8 in AGS and HGC27 cell lines were higher than those in normal cells, while E2F7 showed the opposite trend. Conclusions In summary, these results indicate that E2F1/2/3/4/5 can be used as potential therapeutic targets in gastric cancer, and E2F6/7/8 can be used as new prognostic markers to improve the survival rate and prognostic accuracy in gastric cancer.