卵巢癌潜在细胞周期相关靶基因生物信息学分析

Bioinformatics Analysis of Potential Cell Cycle-related Target Genes in Ovarian Cancer

目的通过生物信息学方法探索卵巢癌相关关键基因及信号通路。方法从GEO数据库中筛选并下载4个基因表达数据集,通过GEO2R筛选共同差异表达基因,利用g:profiler在线平台对共同差异基因进行基因本体和京都基因与基因组百科全书富集分析,采用STRING数据库及Cytoscape软件进行蛋白质-蛋白质互作网络构建和关键基因筛选,通过Kaplan-Meier数据库对关键基因进行生存分析,使用GEPIA及Oncomine数据库进行关键基因表达水平验证。结果共筛选出137个与卵巢癌相关的共同差异表达基因,包括101个共同上调基因和36个共同下调基因。富集分析显示,差异基因主要参与调控细胞有丝分裂和细胞周期。Kaplan-Meier生存分析筛选出7个与卵巢癌患者总生存期及无进展生存期呈负相关的细胞周期相关关键基因:细胞周期蛋白B1、着丝粒蛋白F、中心体相关蛋白55、人类异常纺锤体样小头畸形相关蛋白基因、DNA修复相关蛋白51连接蛋白1、驱动蛋白家族成员11以及苯并咪唑出芽抑制解除同源物蛋白1,均在卵巢癌组织中高表达。结论细胞周期相关因子异常表达导致的细胞周期紊乱可能是卵巢癌发生的重要机制,卵巢癌细胞周期紊乱相关关键基因可能是卵巢癌潜在的药物研发靶点。

Objective To explore key genes and signaling pathways related to ovarian cancer via bioinformatics analysis.Methods Four gene expression data sets were selected and downloaded from the GEO database;the common differentially expressed genes were screened by GEO2R tool;the common differentially expressed genes were analyzed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis via the g:profiler online platform;protein-protein interaction network establishment and key genes screening were done through STRING database and Cytoscape software;survival analysis of key genes was conducted via Kaplan-Meier database,and the expression levels of key genes were confirmed by GEPIA and Oncomine database.Results A total of 137 co-differentially expressed genes related to ovarian cancer were screened out,including 101 co-upregulated genes and 36 co-downregulated genes.Gene enrichment analysis showed that the differentially expressed genes were mainly related to cell mitosis,and cell cycle.7 cell cycle related key genes were screened out via Kaplan-Meier analysis,which were negatively correlated with overall survival and progression-free survival of ovarian cancer patients.The 7 key genes included cyclin B1,centromere protein F,centrosomal protein 55,assembly factor for spindle microtubules,DNA repair associated protein RAD51 connexin 1,kinesin family member 11 and benzimidazoles bud inhibition release homologue protein 1,all of which were over-expressed in ovarian cancer tissues.Conclusion The cell cycle disorder caused by abnormal expression of cell cycle related factors may be an important mechanism for the occurrence of ovarian cancer,and cell cycle disorder related key genes may be potential targets for the drug research and development of ovarian cancer.