Comprehensive Analysis of the Expression and Prognosis for E2Fs in Human Clear Cell Renal Cell Carcinoma

Abstract

Background. E2F transcription factors is a family of transcription factors, and lots of studies have shown that they play a key role in the occurrence and development of many tumors. However, the association between expression, prognostic value, and immune infiltration in the tumor microenvironment of the eight E2Fs members in ccRCC is still unclear. Methods. We used online databases, such as ONCOMINE, UALCAN, Kaplan–Meier plotter, GEPIA, Metascape, TIMER, and cBioPortal, to analyze the effect of mRNA expression of E2Fs family members in ccRCC on the prognosis of patients and the relationship with immune infiltration. Results. Except for E2F5, other seven members of the family of E2Fs mRNA expression levels in ccRCC tissues were significantly higher than control tissues. And the high expression of E2Fs mRNA in ccRCC patients was related to cancer stage and tumor grade. Survival analysis results suggested that elevated mRNA expression levels of E2F1/2/3/4/7/8 were significantly related to the shorter overall survival (OS) in ccRCC patients ( P = 3.9E – 06), while high mRNA expression of E2F6 is not related to OS ( P = 0.061). Mutations of E2Fs were correlated with shorter OS of ccRCC patients ( P = 7.094E – 5). In addition, mRNA expression of E2F1/2/3/4/7/8 was positively correlated with infiltration of six types of immune cells, including B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells. Conclusions. These results indicate that E2F1/2/3/4/7/8 may be used as a prognostic marker for the survival of ccRCC patients and laid the foundation for studying the immune infiltration role of E2Fs family members in tumors.

Biomarker analysis from CheckMate 214: nivolumab plus ipilimumab versus sunitinib in renal cell carcinoma

“…For example, expression of transcripts corresponding to MYC and E2F targets were negatively associated with OS in both treatment arms, supporting the association of E2F-driven and MYC-driven gene expression with poor prognosis in patients with RCC. [46][47][48] While the association of the HALLMARK fatty acid metabolism gene set with response to sunitinib is in accordance with previously reported data, 49 the current study shows that enrichment of the same gene set is also associated with prolonged survival with nivolumab plus ipilimumab, supporting the hypothesis that expression of genes involved in fatty acid metabolism is a prognostic biomarker for RCC. 50 This is in contrast to the negative correlation between the HALLMARK fatty acid metabolism gene set and response to nivolumab monotherapy in CheckMate 009, where the majority of patients had received prior therapy with VEGF inhibitors.…”

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

“…E2F1 mRNA expression level is related to pathological parameters and is an independently unfavorable factor for OS in clear cell renal cell carcinoma (51). Although E2F1 is one of the most researched E2Fs family members (52), the exact role of E2F1 in LIHC remains controversial and unsettled. It is reported that E2F1 is upregulated in LICH and promotes the development of LIHC via targeting MYBL2 or through being regulated by SIRT5 (15,53).…”

The Role of transcription factor FOXA1/C2/M1/O3/P1/Q1 in breast cancer

“…The Cancer Genome Atlas (TCGA) database is a publicly available database of tumor gene information, containing high-throughput sequencing and pathological data for 30 different cancers. A large number of cancer gene maps can be systematically analyzed to nd out the similarities and differences in the genomic architecture of each cancer and across multiple types (27,28). cBioportal (www.cbioportal.org) is a comprehensive online open source that provides us with visualized and multidimensional cancer genomic data.…”