基于生物信息学筛选并分析男性肝癌患者发病中的关键基因

Screening and analysis of key genes in male patients with liver cancer based on bioinformatics

摘+要:目的筛选男性肝癌患者中的差异基因并分析探讨其对不同性别患者预后的影响。方法在GEO数据库中获取男性肝癌患者的基因表达数据,通过GEO2R在线工具获取差异基因(DGEs)并在DAVIAD数据库中进行GO和KEGG富集分析;STRING数据库中进行差异基因网络互作分析(PPI),结合Ctoscape插件Cytohubaba获取前10位的关键基因,并且在GEPIA、Kaplan-Meier plotter数据库中分析其对不同患者预后的影响。结果从GSE19665与GSE84002中分别筛选出男性患者与健康对照者的差异基因并取交集,最终得到162个DGEs;使用DAVID网站对DGEs进行聚类分析,GO功能富集分析显示DGEs主要参与细胞分裂、胞外区、铁离子结合等过程;KEGG分析显示DGEs主要参与细胞周期、卵母细胞减数分裂、p53等信号通路;使用STRING网站对DGEs做PPI网络互作分析,并用Ctoscape软件的MCODE和CytoHubba两个APP从PPI网络中分解关键网络分析核心基因获取了10个关键基因(CDCA8,CCNB2,BUB1,KIF20A,DLGAP5,BIRC5,CDC20,CDK1,ASPM,TOP2A);使用GEPIA网站查询得知TCGA数据中的核心基因均高表达;使用Kaplan-Meier plotter网站分析,细胞周期蛋白B2(recombinant cyclin B2,CCNB2)和有丝分裂相关基因(abnormal spidle microtubule assembly,ASPM)两个基因高表达且与男性患者预后差相关。结论与女性肝癌患者相比,CCNB2和ASPM的高表达与男性肝癌患者整体生存期显著相关,可作为男性肝癌患者早期诊断和个性化治疗的靶向分子标志物。

Objective To screen the differential genes in male liver cancer and explore their effects on the prognosis of patients of different genders.Methods Gene expression data of male patients with liver cancer were obtained in GEO database.Differential genes(DGEs) were obtained through GEO2 R online tool,and GO and KEGG enrichment analysis were carried out in DAVID database.Perform network interaction analysis protein-protein interaction(PPI) in the STRING database,combined with the Ctoscape plug-in Cytohubaba to obtain the top 10 key genes,and analyze their impact on the prognosis of different patients in the GEPIA and Kaplan-Meier plotter databases.Results From GSE19665 and GSE84002,the differential genes between male patients and normal patients were screened out and crossed,and finally 162 DGEs were obtained.Cluster analysis of DGEs was performed on the DAVID website.GO functional enrichment analysis showed that DGEs were mainly involved in cell division,extracellular domain,iron binding and other processes.KEGG analysis showed that DGEs were mainly involved in signal pathways such as cell cycle,oocyte meiosis,and p53.Use STRING website to do PPI network interaction analysis on DGEs,and use Ctoscape software’s MCODE and CytoHubba APP to decompose key network analysis core genes from PPI network,and obtain 10 key genes(CDCA8,CCNB2,BUB1,KIF20A,DLGAP5,BIRC,CDC,CDK,ASPM,TOP2A).GEPIA website query was used to know that the core genes in the TCGA data were all highly expressed.Kaplan-Meier plotter website analysis and screening showed that the high expression of CCNB2 and ASPM genes was only related to the poor prognosis of male patients.Conclusion Compared with female liver cancer patients,the high expression of CCNB2 and ASPM was significantly correlated with the overall survival of male patients.It can be used as targeted molecular markers for early diagnosis and personalized treatment of male liver cancer patients.