基于生物信息学识别早期肺腺癌生物标志物  

Identification of potential biomarkers of early-stage lung adenocarcinoma based on bioinformatics

作　　者：苗桂华 袁金珊 李德涛[1] 侯玉磊[1] 陈辉[1] MIAO Guihua;YUAN Jinshan;LI Detao;HOU Yulei;CHEN Hui(Department of Clinical Laboratory,the First Affiliated Hospital of Chongqing Medical University,Chongqing 400016,China)

机构地区：[1]重庆医科大学附属第一医院医学检验科,重庆400016

出　　处：《国际检验医学杂志》2023年第19期2324-2330,共7页International Journal of Laboratory Medicine

基　　金：重庆市2021年科卫联合医学科研项目(2021MSXM095)。

摘　　要：目的通过生物信息学分析,探索用于肺腺癌早期诊断的潜在生物标志物。方法采用生物信息学方法,选择早期肺腺癌的基因表达数据库(GEO)数据集GSE27262、GSE63459、GSE116959、GSE118370,筛选肺腺癌与正常样本之间的差异表达基因,选择DAVID在线分析工具进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)分析,使用STRING和Cytoscape绘制蛋白质-蛋白质相互作用(PPI)网络图,使用cytoHubba确认PPI网络的中枢基因,并通过GEPIA2数据库验证中枢基因的表达和总生存率。结果共获得154个差异表达基因,主要集中于血管新生、细胞膜筏、转化生长因子-β(TGF-β)结合功能和肿瘤组织中的蛋白聚糖;创建了一个由154个节点和195条边组成的PPI网络;采用最大集团中心度(MCC)算法筛选出10个中枢基因:PECAM1、ENG、VWF、TEK、TIMP1、CAV1、ANGPT1、ACVRL1、BMPR2和SMAD6。除TIMP1外,这些中枢基因在肺腺癌组织中的表达均下调。生存分析结果显示,PECAM1和ENG的低水平表达与肺腺癌患者的不良总生存率有关。结论PECAM1和ENG与肺腺癌患者的血管生成有关,可作为肺腺癌的早期生物标志物。Objective To explore the potential novel biomarkers for early detection of lung adenocarcinoma by bioinformatics analysis.Methods Gene Expression Ominbus(GEO)series GSE27262,GSE63459,G SE116959 and GSE118370 of early lung adenocarcinoma were selected by bioinformatics method.Differential expression genes between lung adenocarcinoma and normal samples were screened.Gene Ontology(GO)and the Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis were performed by DAVID online analysis tools.STRING and Cytoscape were applied to plot a protein-protein interaction(PPI)network.Hub genes of the PPI network were confirmed using cytoHubba and hub genes expression and overall survival rates were validated by using GEPIA2 database.Results A total of 154 differentially expressed genes were obtained,which mainly focused on angiogenesis,cell membrane raft,transforming growth factor-β(TGF-β)binding function and proteoglycan in tumor tissues.A PPI network consisting of 154 nodes and 195 edges was created.Ten hub genes were filtered in the manner of the maximal clique centrality(MCC),including PECAM1,ENG,VWF,TEK,TIMP1,CAV1,ANGPT1,ACVRL1,BMPR2 and SMAD6.Except for TIMP1,the expres sion of these central genes was down-regulated in lung adenocarcinoma tissues.Survival analysis showed that low levels of PECAM1 and ENG expression were associated with poor OS in patients with lung adenocarcinoma.Conclusion PE CAM1 and ENG should be involved in the angiogenesis of lung adenocarcinoma,and might be used as early-stage biomarkers of lung adenocarcinoma.

关 键 词：肺腺癌 生物信息学 生物标志物 PECAM1 ENG 

分 类 号：R734.2[医药卫生—肿瘤] Q811.4[医药卫生—临床医学]