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Gastric cancer (GC) is the second most common cancer and the third most frequent cause of cancer-related deaths in China. E2Fs are a family of transcription factors reported to be involved in the tumor progression of various cancer types; however, the roles of individual E2Fs are still not known exactly in tumor progression of GC. In this study, we examined the expression of E2Fs to investigate their roles in tumor progression in GC patients using multiple databases, including ONCOMINE, GEPIA2, Kaplan-Meier plotter, cBioPortal, Metascape, LinkedOmics, GeneMANIA, STRING and UCSC Xena. We also performed real-time polymerase chain reaction (RT-PCR) to validate the expression levels of individual E2Fs in several GC cell lines. Our results demonstrated that the mRNA levels of  E2F1/2/3/5/8  were significantly higher both in GC tissues and cell lines. The expression levels of  E2F1  and  E2F4  were correlated with poor overall survival (OS), decreased post-progression survival (PPS), and decreased progression-free survival (FP) in patients with GC. However, overexpression of  E2F2 ,  E2F5 ,  E2F7  and  E2F8  is significantly associated with disease-free survival and overall survival in patients with GC. In addition, higher  E2F3  and  E2F6  mRNA expression was found to increase GC patients’ OS and PPS. 224 of 415 patients with STAD (54%) had gene mutations that were associated with longer disease-free survival (DFS) but not OS. Cell cycle pathway was closely associated with mRNA level of more than half of E2Fs ( E2F1/2/3/7/8 ). There were close and complicated interactions among E2F family members. Finally, our results indicated the gene expressions of E2Fs had a positive relationship with its copy numbers. Taken together,  E2F1/2/3/5/8  can serve as biomarkers for GC patients with high prognostic value for OS of GC patients or therapeutic targets for GC.

Comprehensive Analysis of E2F Family Members in Human Gastric Cancer