Differential Expression of E2F Transcription Factors and Their Functional and Prognostic Roles in Human Prostate Cancer

Zhaodong Han; Rujun Mo; Shanghua Cai; Yuanfa Feng; Zhenfeng Tang; Jianheng Ye; Ren Liu; Zhiduan Cai; Xuejin Zhu; Yulin Deng; Zhihao Zou; Yongding Wu; Zhouda Cai; Yuxiang Liang; Weide Zhong

doi:10.3389/fcell.2022.831329

Differential Expression of E2F Transcription Factors and Their Functional and Prognostic Roles in Human Prostate Cancer

Front Cell Dev Biol. 2022 Apr 21:10:831329. doi: 10.3389/fcell.2022.831329. eCollection 2022.

Authors

Zhaodong Han¹, Rujun Mo², Shanghua Cai³, Yuanfa Feng³, Zhenfeng Tang³, Jianheng Ye¹, Ren Liu¹, Zhiduan Cai⁴, Xuejin Zhu⁵, Yulin Deng^{1

3}, Zhihao Zou¹, Yongding Wu¹, Zhouda Cai⁶, Yuxiang Liang¹, Weide Zhong^{1

3}

Affiliations

¹ Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China.
² Department of Urology, Affiliated Dongguan Hospital, Southern Medical University, Dongguan, China.
³ Department of Urology, Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.
⁴ Department of Urology, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
⁵ Department of Urology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.
⁶ Department of Andrology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China.

Abstract

Given the tumor heterogeneity, most of the current prognostic indicators cannot accurately evaluate the prognosis of patients with prostate cancer, and thus, the best opportunity to intervene in the progression of this disease is missed. E2F transcription factors (E2Fs) have been reported to be involved in the growth of various cancers. Accumulating studies indicate that prostate cancer (PCa) carcinogenesis is attributed to aberrant E2F expression or E2F alteration. However, the expression patterns and prognostic value of the eight E2Fs in prostate cancer have yet to be explored. In this study, The Cancer Genome Atlas (TCGA), Kaplan-Meier Plotter, Metascape, the Kyoto Encyclopedia of Genes and Genomes (KEGG), CIBERSORT, and cBioPortal and bioinformatic analysis were used to investigate E2Fs in patients with PCa. Our results showed that the expression of E2F1-3, E2F5, and E2F6 was higher in prostate cancer tissues than in benign tissues. Furthermore, elevated E2F1-3 and E2F5 expression levels were associated with a higher Gleason score (GS), advanced tumor stage, and metastasis. Survival analysis suggested that high transcription levels of E2F1-3, E2F5, E2F6, and E2F8 were associated with a higher risk of biochemical recurrence. In addition, we developed a prognostic model combining E2F1, E2F6, Gleason score, and the clinical stage that may accurately predict a biochemical recurrence-free survival. Functional enrichment analysis revealed that the E2F family members and their neighboring genes were mainly enriched in cell cycle-related pathways. Somatic mutations in different subgroups were also investigated, and immune components were predicted. Further experiments are warranted to clarify the biological associations between Pca-related E2F family genes, which may influence prognosis via the cell cycle pathway.

Keywords: E2F transcription factors; biochemical recurrence; bioinformatic analysis; prognosis; prostate cancer.