Rasti Azam, Abazari Omid, Dayati Parisa, Kardan Zahra, Salari Ali, Khalili Masoud, Motlagh Fatemeh Movahedi, Modarressi Mohammad Hossein
Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Department of Clinical Biochemistry, School of Medicine, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran.
Adv Biomed Res. 2023 Jun 28;12:157. doi: 10.4103/abr.abr_280_22. eCollection 2023.
Growing evidence strongly indicates pivotal roles of gender differences in the occurrence and survival rate of patients with bladder cancer, with a higher incidence in males and poorer prognosis in females. Nevertheless, the molecular basis underlying gender-specific differences in bladder cancer remains unknown. The current study has tried to detect key genes contributing to gender differences in bladder cancer patients.
The gene expression profile of GSE13507 was firstly obtained from the Gene Expression Omnibus (GEO) database. Further, differentially expressed genes (DEGs) were screened between males and females using R software. Protein-protein interactive (PPI) network analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and Kaplan-Meier survival analyses were also performed.
We detected six hub genes contributing to gender differences in bladder cancer patients, containing IGF2, CCL5, ASPM, CDC20, BUB1B, and CCNB1. Our analyses demonstrated that CCNB1 and BUB1B were upregulated in tumor tissues of female subjects with bladder cancer. Other genes, such as IGF2 and CCL5, were associated with a poor outcome in male patients with bladder cancer. Additionally, three signaling pathways (focal adhesion, rheumatoid arthritis, and human T-cell leukemia virus infection) were identified to be differentially downregulated in bladder cancer versus normal samples in both genders.
Our findings suggested that gender differences may modulate the expression of key genes that contributed to bladder cancer occurrence and prognosis.
越来越多的证据有力地表明，性别差异在膀胱癌患者的发生和生存率中起关键作用，男性发病率较高，女性预后较差。然而，膀胱癌性别特异性差异的分子基础仍然未知。当前研究试图检测导致膀胱癌患者性别差异的关键基因。
首先从基因表达综合数据库（GEO）中获取GSE13507的基因表达谱。此外，使用R软件筛选男性和女性之间的差异表达基因（DEG）。还进行了蛋白质-蛋白质相互作用（PPI）网络分析、京都基因与基因组百科全书（KEGG）、基因本体论（GO）以及Kaplan-Meier生存分析。
我们检测到六个导致膀胱癌患者性别差异的枢纽基因，包括胰岛素样生长因子2（IGF2）、趋化因子配体5（CCL5）、异常纺锤体样微管相关蛋白（ASPM）、细胞周期蛋白依赖性激酶20（CDC20）、BUB1有丝分裂检查点蛋白B（BUB1B）和细胞周期蛋白B1（CCNB1）。我们的分析表明，CCNB1和BUB1B在女性膀胱癌患者的肿瘤组织中上调。其他基因，如IGF2和CCL5，与男性膀胱癌患者的不良预后相关。此外，还确定了三条信号通路（粘着斑、类风湿性关节炎和人类T细胞白血病病毒感染）在两性的膀胱癌与正常样本中差异下调。
我们的研究结果表明，性别差异可能调节导致膀胱癌发生和预后的关键基因的表达。
