Research Article: Transcriptional E2F1/2/5/8 as potential targets and transcriptional E2F3/6/7 as new biomarkers for the prognosis of human lung carcinoma

Date Published: May 11, 2018

Publisher: Impact Journals

Author(s): Cheng-Cao Sun, Qun Zhou, Wei Hu, Shu-Jun Li, Feng Zhang, Zhen-Long Chen, Guang Li, Zhuo-Yue Bi, Yong-Yi Bi, Feng-Yun Gong, Tao Bo, Zhan-Peng Yuan, Wei-Dong Hu, Bo-Tao Zhan, Qian Zhang, Qi-Zhu Tang, De-Jia Li.


E2F is a group of genes that encode a family of transcription factors (TFs) in higher eukaryotes and participate in cell cycle regulation and DNA synthesis in mammalian cells. Evidence from cell lines, mouse models, and human tissues indicates that TFs are implicated in lung cancer (LC) tumorigenesis. However, the diverse expression patterns and prognostic values of eight E2Fs have yet to be elucidated. In the current study, we examined the transcriptional and survival data of E2Fs in patients with LC from ONCOMINE, GEPIA, Kaplan–Meier Plotter, and cBioPortal databases. We found that the expression levels of E2F1/2/3/5/6/7/8 were higher in lung adenocarcinoma and squamous cell lung carcinoma tissues than in lung tissues, whereas the expression level of E2F4 was lower in the former than in the latter. The expression levels of E2F2/4/5/7/8 were correlated with advanced tumor stage. Survival analysis using the Kaplan–Meier Plotter database revealed that the high transcription levels of E2F1/2/4/5/7/8 were associated with low relapse-free survival (RFS) in all of the patients with LC. Conversely, high E2F3/6 levels predicted high RFS in these patients. This study implied that E2F3/6/7 are potential targets of precision therapy for patients with LC and that E2F1/2/4/5/8 are new biomarkers for the prognosis of LC.

Partial Text

E2Fs, a group of genes that encode a family of transcription factors (TFs) in higher eukaryotes, are generally subdivided into two groups based on functions: transcriptional activators (E2F1, E2F2, and E2F3a) and transcriptional repressors (E2F3b and E2F4-8) [1]. E2F family members play a major role in cell cycle regulation and DNA synthesis in mammalian cells [2]. The expression of E2F activators is deregulated in several human malignancies, including bladder cancer [3], breast cancer [4], ovarian cancer [5], prostate cancer [5], gastrointestinal cancer [6], and lung cancer [7,8].

E2F factors dysregulation has been reported in many cancers [2,29–31]. Although the role of E2F activators in the tumorigenesis and prognosis of several cancers has been partially confirmed [7,18,19], further bioinformatics analysis of LC has yet to be performed. The present study is the first time to explore the mRNA expression and prognostic (OS, FP, and PPS) values of different E2F factors in LC. We hope that our findings will contribute to available knowledge, improve treatment designs, and enhance the accuracy of prognosis for patients with LC.




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