Identification and functional analysis of pathogenic genes and key transcription factors in prostate adenocarcinoma
10.3872/j.issn.1007-385x.2020.10.011
- VernacularTitle:前列腺癌中致病基因与核心转录因子的识别与功能分析
- Author:
HUANG Qingqing
1
;
TAN Zhengtang
1
;
LI Changying
1
;
QIU Zhengliang
2
;
GUO Zhiyun
1
Author Information
1. 1. School of Life Science and Engineering,Southwest Jiaotong University, Chengdu 610031, Sichuan, China
2. 2. Laboratory Animal Center, Academy of Military Medical Sciences, Beijing 100071, China
- Publication Type:Journal Article
- Keywords:
weighted gene co-expression network analysis (WGCNA);
prostate adenocarcinoma;
transcription factor;
signaling pathway
- From:
Chinese Journal of Cancer Biotherapy
2020;27(10):1138-1143
- CountryChina
- Language:Chinese
-
Abstract:
[Abstract] Objective: To investigate the pathogenesis of prostate cancer by analyzing the associated hub gene modules of prostate
cancer and identifying key transcription factors and genes that affect these modules. Methods: WGCNA (weighted gene co-expressed
network analysis) was used to identify hub gene modules associated with important clinicopathological features of prostate cancer, such
as pathological staging, Gleason grading etc. The OPOSSUM online tool was used to analyze the transcription factors enriching and
regulating those genes. Pathway enrichment analysis and protein-protein interaction network analysis were used to identify key genes in
prostate cancer. Finally, the effects of these genes on clinical features and disease-free survival (DFS) of prostate cancer patients were
analyzed. Results: Three hub modules were identified, and they were highly associated with pathologic T stage, pathologic N stage and
Gleason grading of prostate cancer, respectively. Further screening revealed 13 key dysregulated transcription factors that participated
in the regulation of these three hub modules. The differentially expressed genes regulated by the 13 key transcription factors were
significantly enriched in Calcium signaling pathway, cGMP-PKG signaling pathway and cAMP signaling pathway. 14 key genes
(PRKG1, PRKG2, CYSLTR2, GRPR, CHRM3, ADCY5, ADRA1D, EDNRA, EDNRB, CYSLTR2, AGTR1, GRPR, GRIA1 and OXT)
were at important nodes in the gene network. Among them, the high expression of ADRA1A, PRKG2, CHRM3, ADRA1D and EDN3
significantly extended the DFS of patients with prostate cancer (all P<0.01). Conclusion: ADRA1A, PRKG2, CHRM3, ADRA1D and
EDN3 are regulated by key dysregulated transcription factors and highly associated with clinical features of prostate cancer. Their high
expressions will significantly prolong the DFS of prostate cancer patients, which may shed light to the discovery of mechanism in prostate adenocarcinoma.
- Full text:20201011.pdf
