Lai Yo-Liang, Liu Chia-Hsin, Wang Shu-Chi, Huang Shu-Pin, Cho Yi-Chun, Bao Bo-Ying, Su Chia-Cheng, Yeh Hsin-Chih, Lee Cheng-Hsueh, Teng Pai-Chi, Chuu Chih-Pin, Chen Deng-Neng, Li Chia-Yang, Cheng Wei-Chung
Graduate Institute of Biomedical Science, China Medical University, Taichung 40403, Taiwan.
Department of Radiation Oncology, China Medical University Hospital, Taichung 40403, Taiwan.
Cancers (Basel). 2022 Mar 19;14(6):1565. doi: 10.3390/cancers14061565.
The importance of anti-androgen therapy for prostate cancer (PC) has been well recognized. However, the mechanisms underlying prostate cancer resistance to anti-androgens are not completely understood. Therefore, identifying pharmacological targets in driving the development of castration-resistant PC is necessary. In the present study, we sought to identify core genes in regulating steroid hormone pathways and associating them with the disease progression of PC. The selection of steroid hormone-associated genes was identified from functional databases, including gene ontology, KEGG, and Reactome. The gene expression profiles and relevant clinical information of patients with PC were obtained from TCGA and used to examine the genes associated with steroid hormone. The machine-learning algorithm was performed for key feature selection and signature construction. With the integrative bioinformatics analysis, an eight-gene signature, including , , , , , , , and was established. Patients with higher expression of this gene signature had worse progression-free interval in both univariate and multivariate cox models adjusted for clinical variables. The expression of the gene signatures also showed the aggressiveness consistently in two external cohorts, PCS and PAM50. Our findings demonstrated a validated eight-gene signature could successfully predict PC prognosis and regulate the steroid hormone pathway.
抗雄激素疗法对前列腺癌(PC)的重要性已得到充分认可。然而,前列腺癌对抗雄激素耐药的潜在机制尚未完全明确。因此,确定驱动去势抵抗性前列腺癌发展的药理学靶点很有必要。在本研究中,我们试图鉴定调节类固醇激素途径的核心基因,并将它们与前列腺癌的疾病进展相关联。类固醇激素相关基因的选择来自功能数据库,包括基因本体论、KEGG和Reactome。前列腺癌患者的基因表达谱和相关临床信息从TCGA获得,并用于检测与类固醇激素相关的基因。采用机器学习算法进行关键特征选择和特征构建。通过综合生物信息学分析,建立了一个包括[具体基因未给出]、[具体基因未给出]、[具体基因未给出]、[具体基因未给出]、[具体基因未给出]、[具体基因未给出]、[具体基因未给出]和[具体基因未给出]的八基因特征。在针对临床变量进行调整的单变量和多变量cox模型中,该基因特征表达较高的患者无进展生存期较差。该基因特征的表达在两个外部队列PCS和PAM50中也一致显示出侵袭性。我们的研究结果表明,一个经过验证的八基因特征可以成功预测前列腺癌的预后并调节类固醇激素途径。