基于生物信息学分析的肺腺癌诊断及预后相关基因筛选

Screening of Genes Related to Diagnosis and Prognosis of Lung Adenocarcinoma Based on Bioinformatics Analysis

本文运用生物信息学方法分析肺腺癌潜在的诊断及预后基因,并从分子和蛋白水平上探究其潜在的发病机制。从基因表达数据库(GEO)下载GSE63459、GSE27262和GSE75037的表达数据,将3个微阵列数据集整理取得差异表达基因,得出包括上调82个、下调273个的差异基因,并通过DAVID数据挖掘平台对这些差异基因进行功能及通路富集分析。基因本体(GO)富集分析显示:基因产物与胶原蛋白分解代谢、血管生成以及细胞黏附等生物过程密切相关,主要参与组成细胞外基质、胞外区域、胞外体、胶原三聚体等细胞组分,且主要发挥调节金属内肽酶活性、肝素结合、调节受体活性等分子功能;京都基因基因组百科全书(KEGG)分析主要涉及胞外基质-受体信号通路、黏着斑信号通路、转化生长因子-β(TGF-β)信号通路、磷脂酰肌醇-3-激酶(PI3K-Akt)信号通路等相关通路。运用STRING在线数据库并结合Cytoscape软件构建蛋白-蛋白互助(PPI)网络,筛选出最重要的基因模块及10个关键基因,利用Kaplan-Meier曲线分析预后,利用GEPIA和THPA在线数据库从基因和蛋白水平来验证分析关键基因与患者的预后关系。最后筛选到符合条件的4个肺腺癌关键基因:SPP1、TIMP1、MMP9、COL1A1。这4个基因可能成为肺腺癌预后潜在的生物标志物,并有可能成为治疗靶点和诊断靶标,对临床上肺腺癌的诊断和治疗有一定价值。

To analyze the microarray data to screen its potential pathogenesis at the molecular level,and explore the potential biomarkers of lung adenocarcinoma(LUAD).The expression data of GSE63459,GSE27262 and GSE75037 were downloaded from the Gene Expression Omnibus(GEO),and the differentially expressed genes were obtained from three microarray datasets,including 82 up-regulated genes and 273 down-regulated genes.The function and pathway enrichment of these differential genes were analyzed by DAVID data mining platform.Gene ontology(GO)enrichment analysis showed that the gene products were closely related to collagen catabolism,angiogenesis,cell adhesion and other biological processes,mainly involved in the composition of extracellular matrix,extracellular region,extracellular body,collagen trimer and other cellular components,and mainly played a role in regulating the activity of metalloendopeptidase,heparin binding,regulation of receptor activity and other molecular functions.Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis mainly involves extracellular matrix-receptor signal pathway,adhesion spot signal pathway,TGF-βsignal pathway,PI3K-Akt signal pathway and other related pathways.Then the protein-protein interaction(PPI)network was constructed by using STRING online database and Cytoscape software,and the most important gene modules and 10 key genes were screened.Then the prognosis was analyzed by Kaplan-Meier plotter,and the relationship between key genes and prognosis was verified and analyzed by GEPIA and THPA online database from gene and protein level.Finally,four key genes of lung adenocarcinoma(LUAD)were screened:SPP1,TIMP1,MMP9 and COL1A1.These four genes may become potential biomarkers of prognosis of lung adenocarcinoma,and may become therapeutic targets and diagnostic targets,which have certain value for clinical diagnosis and treatment of LUAD.