Liu Shiyun, Huang Da, Huang Jingyi, Yan Jiaqi, Chen Tianhe, Zhang Ning, Jiang Guangliang, Gao Yi, Xu Danfeng, Na Rong
Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China.
J Cancer. 2021 Feb 22;12(8):2173-2180. doi: 10.7150/jca.50299. eCollection 2021.
Mechanism of castration-resistant prostate cancer (CRPC) is still unclear. Our objective is to investigate the association between genes expression and CRPC through the genome-wide approach and functional researches. Differentially expressed genes (DEGs) between PCa and CRPC tissues were identified using expression profile obtained from Gene Expression Omnibus database (GEO). Survival analysis was performed using online database Gene Expression Profiling Interactive Analysis (GEPIA). Oncomine database was further used to explore the relationship between DEGs expression levels with clinical parameters. After study, SEC14L2-knockdown CRPC cells and normal prostatic epithelial cells were used for study to verify its biological functions. A total of 3 consistently changed DEGs (SEC14L2, DMD, SEL1L) were identified correlating with CRPC after cross validation in three independent datasets. Low expression of SEC14L2 was associated with poorer disease-free survival and higher Gleason score than normal/high expression of SEC14L2. SEC14L2 knockdown promoted cell proliferation, migration, invasion as well as cell cycle progression in CRPC cells (all P<0.05) while no significant effects were observed in normal prostatic epithelial cells. Low expression of SEC14L2 was significantly associated with CRPC, and correlated with PCa aggressiveness and poorer prognosis. SEC14L2 might be a potential biomarker or drug target for CRPC.
去势抵抗性前列腺癌（CRPC）的机制仍不清楚。我们的目标是通过全基因组方法和功能研究来探究基因表达与CRPC之间的关联。利用从基因表达综合数据库（GEO）获得的表达谱，鉴定前列腺癌（PCa）组织和CRPC组织之间的差异表达基因（DEGs）。使用在线数据库基因表达谱交互式分析（GEPIA）进行生存分析。进一步利用Oncomine数据库探索DEGs表达水平与临床参数之间的关系。研究后，使用SEC14L2基因敲低的CRPC细胞和正常前列腺上皮细胞进行研究以验证其生物学功能。在三个独立数据集中进行交叉验证后，共鉴定出3个与CRPC相关的一致性变化的DEGs（SEC14L2、DMD、SEL1L）。与SEC14L2正常/高表达相比，SEC14L2低表达与无病生存期较差和Gleason评分较高相关。SEC14L2基因敲低促进了CRPC细胞的增殖、迁移、侵袭以及细胞周期进程（所有P<0.05），而在正常前列腺上皮细胞中未观察到显著影响。SEC14L2低表达与CRPC显著相关，并与PCa的侵袭性和较差预后相关。SEC14L2可能是CRPC的潜在生物标志物或药物靶点。
