Comprehensive Analysis of E2F Family Members in Human Gastric Cancer

Abstract

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.

Inhibition of HDACs Suppresses Cell Proliferation and Cell Migration of Gastric Cancer by Regulating E2F5 Targeting BCL2

“…Moreover, the inhibition of HDAC appearance can relatively invalidate the E2F5-mediated results in gastric tumor cells, and re-establish cell proliferation invasion and migration. Therefore, these results demonstrate that the expression of HDACi may perhaps be involved in cancer development and progression in gastric tumor carcinogenesis [2]. The current research intensifies the idea that the lower expression of E2F5 exhausts the inhibitory function of HDAC inhibitor in gastric cells, suggesting that the interaction of E2F5 with BCL2 inhibitors plays a critical part in the anticancer proceedings [19].…”

“…Therefore, prognostic identification of indicators related to malignant tumors of the stomach is important in order to understand the clinical outcomes and distinctive treatment plans for patients with gastric cancer. Histone deacetylases (HDACs) have been illustrated to play a key role corresponding to proliferation, migration, and invasion in different types of cancer [2]. HDACs are an enzyme family, and their activity rules the lysine residues of proteins in the acetylation state, notably those present in the amino-terminal extensions of the core histones.…”

DeepCG: A cell graph model for predicting prognosis in lung adenocarcinoma

“…We have previously developed an E2F4 gene signature that characterizes the downstream pathway activities of E2F4, 14 which is a transcription factor involved in cell cycle regulation 15,16 . Dysfunction in the E2F4 pathway has been found in multiple cancer types 17–19 . We have shown that the E2F4 signature was prognostic in several cancer types, 14,20,21 but its performance in lung cancer has not been evaluated.…”

“…15,16 Dysfunction in the E2F4 pathway has been found in multiple cancer types. [17][18][19] We have shown that the E2F4 signature was prognostic in several cancer types, 14,20,21 but its performance in lung cancer has not been evaluated.…”

E2F1 as a potential prognostic and therapeutic biomarker by affecting tumor development and immune microenvironment in hepatocellular carcinoma

“…A variety of E2F isoforms have been characterized and can be found in most cell types (8). It has been demonstrated that E2F family genes are overexpressed and associated with the development and prognosis in several types of cancers including LIHC (9)(10)(11)(12)(13).…”