Differential Expression of E2F Transcription Factors and Their Functional and Prognostic Roles in Human Prostate Cancer
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 invo...
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Frontiers Media S.A.
2022-04-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2022.831329/full |
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| author | Zhaodong Han Rujun Mo Shanghua Cai Yuanfa Feng Zhenfeng Tang Jianheng Ye Ren Liu Zhiduan Cai Xuejin Zhu Yulin Deng Yulin Deng Zhihao Zou Yongding Wu Zhouda Cai Yuxiang Liang Weide Zhong Weide Zhong |
| author_facet | Zhaodong Han Rujun Mo Shanghua Cai Yuanfa Feng Zhenfeng Tang Jianheng Ye Ren Liu Zhiduan Cai Xuejin Zhu Yulin Deng Yulin Deng Zhihao Zou Yongding Wu Zhouda Cai Yuxiang Liang Weide Zhong Weide Zhong |
| author_sort | Zhaodong Han |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T03:44:18Z |
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| id | doaj.art-783be7f672624342bf987c71174c8ac1 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-10T03:44:18Z |
| publishDate | 2022-04-01 |
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| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-783be7f672624342bf987c71174c8ac12022-12-22T02:03:27ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-04-011010.3389/fcell.2022.831329831329Differential Expression of E2F Transcription Factors and Their Functional and Prognostic Roles in Human Prostate CancerZhaodong Han0Rujun Mo1Shanghua Cai2Yuanfa Feng3Zhenfeng Tang4Jianheng Ye5Ren Liu6Zhiduan Cai7Xuejin Zhu8Yulin Deng9Yulin Deng10Zhihao Zou11Yongding Wu12Zhouda Cai13Yuxiang Liang14Weide Zhong15Weide Zhong16Department 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, ChinaDepartment of Urology, Affiliated Dongguan Hospital, Southern Medical University, Dongguan, ChinaDepartment of Urology, Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, ChinaDepartment of Urology, Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, ChinaDepartment of Urology, Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment of Urology, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaDepartment of Urology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, ChinaDepartment 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, ChinaDepartment of Urology, Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment of Andrology, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment of Urology, Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, ChinaGiven 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.https://www.frontiersin.org/articles/10.3389/fcell.2022.831329/fullprostate cancerE2F transcription factorsprognosisbiochemical recurrencebioinformatic analysis |
| spellingShingle | Zhaodong Han Rujun Mo Shanghua Cai Yuanfa Feng Zhenfeng Tang Jianheng Ye Ren Liu Zhiduan Cai Xuejin Zhu Yulin Deng Yulin Deng Zhihao Zou Yongding Wu Zhouda Cai Yuxiang Liang Weide Zhong Weide Zhong Differential Expression of E2F Transcription Factors and Their Functional and Prognostic Roles in Human Prostate Cancer Frontiers in Cell and Developmental Biology prostate cancer E2F transcription factors prognosis biochemical recurrence bioinformatic analysis |
| title | Differential Expression of E2F Transcription Factors and Their Functional and Prognostic Roles in Human Prostate Cancer |
| title_full | Differential Expression of E2F Transcription Factors and Their Functional and Prognostic Roles in Human Prostate Cancer |
| title_fullStr | Differential Expression of E2F Transcription Factors and Their Functional and Prognostic Roles in Human Prostate Cancer |
| title_full_unstemmed | Differential Expression of E2F Transcription Factors and Their Functional and Prognostic Roles in Human Prostate Cancer |
| title_short | Differential Expression of E2F Transcription Factors and Their Functional and Prognostic Roles in Human Prostate Cancer |
| title_sort | differential expression of e2f transcription factors and their functional and prognostic roles in human prostate cancer |
| topic | prostate cancer E2F transcription factors prognosis biochemical recurrence bioinformatic analysis |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2022.831329/full |
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