Zhang Dongxu, Liang Pu, Wang Qi, Xia Bowen, Yu Liqian, Hu Xiaopeng
Department of Urology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
Institute of Urology, Capital Medical University, Beijing, China.
Front Mol Biosci. 2024 Dec 5;11:1481375. doi: 10.3389/fmolb.2024.1481375. eCollection 2024.
Cancer stem cells are characterized by self-renewal, clonal tumor initiation capacity, and treatment resistance, which play essential roles in the tumor progression of prostate cancer (PCa). In this study, we aim to explore the features of cancer stemness and characterize the expression of stem cell-related genes for PCa.
We downloaded RNA-seq data and related clinical information from The Cancer Genome Atlas (TCGA) database. The mRNA stemness index (mRNAsi) was analyzed for various clinical features, overall survival (OS), and disease-free survival (DFS), and a weighted gene co-expression network analysis (WGCNA) was performed to identify crucial gene modules and key genes, which may play a role in CSCs. The key gene functions were verified using multiple databases, including the TCGA and Gene Expression Omnibus database (GEO). Next, we explored the potential function of the modules and genes obtained using WGCNA using an enrichment analysis. Finally, we performed experiments for further verification.
We found that mRNAsi were higher in PCa tissues than in normal tissues, and the mRNAsi were closely related to the clinical characteristics of PCa. A total of 16 key genes associated with the mRNAsi scores were identified by WGCNA analysis, including NCAPG, NEK2, DLGAP5, CENPA, CENPF, TPX2, GTSE1, KIF4A, NEIL3, CDC25C, UBE2C, CDCA5, MELK, SKA3, NUF2, and BIRC5. These genes were explicitly highly expressed in PCa across TCGA cancers and were validated in 3 independent GEO PCa datasets. The functional annotations of the key genes were linked with the cell proliferation processes. NUF2 may be a potential biomarker for PCa. experiments showed that knockdown NUF2 reduced the proliferation and migration of PCa cells.
The 16 key genes identified in this study significantly correlate with PCa stem cell characteristics and showed prognosis-oriented effects in PCa patients. Further, the NUF2 gene may be used as a drug target for treating PCa.
癌症干细胞具有自我更新、克隆性肿瘤起始能力和治疗抗性等特征，在前列腺癌（PCa）的肿瘤进展中起着至关重要的作用。在本研究中，我们旨在探索癌症干性的特征，并对PCa中干细胞相关基因的表达进行表征。
我们从癌症基因组图谱（TCGA）数据库下载了RNA测序数据和相关临床信息。分析了各种临床特征、总生存期（OS）和无病生存期（DFS）的mRNA干性指数（mRNAsi），并进行了加权基因共表达网络分析（WGCNA）以识别关键基因模块和关键基因，这些基因可能在癌症干细胞中发挥作用。使用包括TCGA和基因表达综合数据库（GEO）在内的多个数据库验证关键基因功能。接下来，我们使用富集分析探索通过WGCNA获得的模块和基因的潜在功能。最后，我们进行实验以进一步验证。
我们发现PCa组织中的mRNAsi高于正常组织，且mRNAsi与PCa的临床特征密切相关。通过WGCNA分析鉴定出总共16个与mRNAsi评分相关的关键基因，包括NCAPG、NEK2、DLGAP5、CENPA、CENPF、TPX2、GTSE1、KIF4A、NEIL3、CDC25C、UBE2C、CDCA5、MELK、SKA3、NUF2和BIRC5。这些基因在TCGA的各类癌症中的PCa中均显著高表达，并在3个独立的GEO PCa数据集中得到验证。关键基因的功能注释与细胞增殖过程相关。NUF2可能是PCa的潜在生物标志物实验表明，敲低NUF2可降低PCa细胞的增殖和迁移。
本研究中鉴定出的16个关键基因与PCa干细胞特征显著相关，并在PCa患者中显示出预后导向作用进一步研究表明，NUF2基因可作为治疗PCa的药物靶点。
