Expressions and prognostic values of the <em>E2F</em> transcription factors in human breast carcinoma

Abstract

E2F transcription factors (E2Fs) are a family of transcription factors involved in cell proliferation, differentiation, and apoptosis. Their important roles in the development and metastasis of breast carcinoma (BC) have been discovered by previous in vitro and in vivo studies. Yet, expressions and distinct prognostic values of these eight E2Fs in human BC remain unclear in many respects. In this study, we aimed to reveal their roles in BC through analyzing the transcription and survival data of the E2Fs in BC patients from four online databases including ONCOMINE, Breast Cancer Gene-Expression Miner v4.1, cBioPortal for Cancer Genomics, and Kaplan–Meier Plotter. We found the overexpression of E2Fs in BC tissues compared with normal breast tissues, except for E2F4. Higher expression levels of E2Fs, except for E2F4 and E2F6, were associated with higher levels of Scarff–Bloom–Richardson grade of BC. Alterations of E2Fs were found to be significantly correlated with poorer overall survival of BC patients. Through plotting the survival curve in the Kaplan–Meier Plotter, it was found that higher mRNA levels of E2F1, E2F3, E2F7, and E2F8 were associated with poorer relapse-free survival in all BC patients, indicating that they are potential targets for individualized treatments of BC patients. Conversely, higher mRNA expression level of E2F4 predicted better RFS in BC patients, suggesting E2F4 as a new biomarker for BC prognosis. Considering currently available limited evidence, further studies need to be performed to investigate the roles of E2Fs in BC.

Evaluation of peripheral blood E2F3 mRNA as a potential diagnostic biomarker in human papillary thyroid cancer

“…By ROC curve analysis, blood E2F3 mRNA was able to effectively distinguish PTC from benign hyperplasia diseases and normal tissue at a cut off 2.30. These ndings were in close agreement with previous studies that demonstrated that peripheral blood E2F3 mRNA may be a diagnostic marker in lung, breast and prostate cancer [18,19,26,31,33,34].…”

“…Moreover, E2F3 plays an important role in determining the time of the G1/S transition and the rate of DNA synthesis [24,25]. Early studies demonstrated that E2F3 is oncogenic in various human cancers, including breast, bladder, lung and prostate cancer [18,19,26]. E2F3 is essential in promoting the proliferation of ovarian cancer cells by initiating integral signaling of the EGFR-driven cell response [27].…”

“…E2F3 is oncogenic in tumorigenesis, and its functions correspond with poor prognosis in many cancers [17]. Early studies showed that E2F3 overexpression is associated with the development of breast, bladder and prostate cancer in humans [18,19]. However, the relationship between E2F3 and human PTC has rarely been reported.…”

Bioinformatics analysis of BUB1 expression and gene regulation network in lung adenocarcinoma

“…It has been reported that the E2F transcription factor is one of the key regulators of cell cycle progression and triggering apoptosis [30]. Also, alterations of E2F may be associated with shorter survival of cancer patients [31]. Moreover, the E2F1 member of the E2F family is associated with metastasis of cancer cells [32].…”

Critical Roles of E2F3 in Growth and Musculo-skeletal Phenotype in Mice

“…Additionally, E2F3 has played a key role in diverse biological processes such as lens development, cardiac neovascularization, DNA damage responses, neuronal migration, and myogenesis [6,13,[17][18][19][20][21]. Dysregulation of E2F3 is closely related to carcinogenesis, and recent studies confirmed that overexpression of miRNAs targeting E2F3, inhibits cell migration and proliferation in many tumors [22][23][24][25][26][27][28]. E2F3 is considered a promising prognostic marker in specific carcinomas [27,29,30].…”