摘要
目的:通过生物信息学方法探讨膀胱癌吉西他滨化疗耐药机制,寻找导致耐药发生的核心基因。方法:通过高通量测序技术筛选差异基因(differentially expressed genes,DEGs),利用GSEA软件获得KEEG信号通路及GO富集分析结果。STRING数据库构建蛋白互作网络,筛选前10位核心基因(高度连接基因)。从筛选的基因中通过Cyto-Hubba插件运用4种不同算法制成蛋白交互韦恩图,筛选出关键核心基因。结果:测序显示DEGs为1157个,上调基因281个,下调基因876个。GO富集分析表明DEGs主要参与了肌系统过程、肌细胞收缩、细胞核分裂等生物学过程。KEEG分析DEGs主要参与的信号通路包括细胞周期、cGMP-PKG、肌肉平滑肌收缩等通路。蛋白-蛋白互作网(PPI network)细胞周期蛋白依赖性激酶抑制因子(cyclin-dependent kinase 1,CDK1)为最核心基因。结论:CDK1可能作为一种调控吉西他滨耐药机制的重要靶基因,可为探究膀胱癌吉西他滨耐药的发病机制、特异性靶点及新靶向药物研发提供理论基础及方向。
Objective To investigate the mechanism of drug resistance to gemcitabine chemotherapy in bladder cancer by bioinformatics method,and to search for the core genes leading to drug resistance.Methods Differentially expressed genes(DEGs)were screened by high-throughput sequencing technology.KEEG signaling pathway and GO enrichment analysis results were obtained by GSEA software.The STRING database was used to construct protein interaction network and screen the top ten core genes.From the top ten genes screened,the Cyto-Hubba plug-in was used to make a protein interaction Venn map using four different algorithms to screen out key core genes.Results Sequencing showed that there were 1157 DEGs,281 up-regulated genes and 876 down-regulated genes.GO enrichment analysis showed that DEGs mainly involved in biological processes such as muscle system,myocyte contraction and nuclear division.KEEG analyzed that the signaling pathways mainly involved in DEGs included cell cycle,cGMP-PKG,smooth muscle contraction and other pathways.The protein-protein interaction network(PPI network)found that cyclin-dependent kinase 1(CDK1)was the most important gene.Conclusion CDK1 may be an important target gene regulating the mechanism of gemcitabine resistance,providing theoretical basis and direction for exploring the pathogenesis,specific targets and research and development of new targeted drugs of bladder cancer gemcitabine resistance.
作者
张阳阳
王磊
胡容珲
韩露露
孙旭东
乔庆东
ZHANG Yangyang;WANG Lei;HU Ronghui;HAN Lulu;SUN Xudong;QIAO Qingdong(Department of Urology,Xinxiang Central Hospital,Xinxiang,Henan,453000,China;Fourth Clinical College,Xinxiang Medical College)
出处
《临床泌尿外科杂志》
CAS
2024年第10期867-870,875,共5页
Journal of Clinical Urology
基金
河南省中青年卫生健康科技创新领军人才培养项目(No:LJRC2023013)
河南省医学科技攻关计划(联合共建)项目(No:LHGJ20210912,LHGJ20220993)。
