非酒精性脂肪性肝病差异表达基因的筛选和生物信息学分析  

Screening and Bioinformatics Analysis of Differentially Expressed Genes in Non-alcoholic Fatty Liver Disease

作　　者：王士宁 程书平 杨丽洁 俞媛洁[1] 吴鹏波[1] 李明[1] 谭诗云[1] WANG Shining;CHENG Shiping;YANG Lijie(Department of Gastroenterology,Renmin Hospital of Wuhan University,Hubei 430060,China)

机构地区：[1]武汉大学人民医院消化内科,430060

出　　处：《医学研究杂志》2023年第8期168-172,167,共6页Journal of Medical Research

摘　　要：目的应用生物信息学方法筛选和分析非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)差异表达关键基因,为NAFLD的预防和治疗提供新的思路。方法从基因表达数据库(Gene Expression Omnibus,GEO)中下载2个NAFLD相关的表达矩阵,分别是GSE48452和GSE63067,利用GEO2R在线分析工具分别筛出健康样本和NAFLD样本差异表达基因(differentially expressed genes,DEGs)(P<0.05,|log_(2)FC|>0.5)。采用R4.1.0软件分别筛选出差异表达上下调基因,做出火山图和热图,对共同的差异表达上下调基因做出Venn图。为了了解DEGs的生物学功能和通路,使用DAVID在线工具分别进行基因本体功能(Gene Ontology,GO)和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)信号通路富集分析,以P<0.05为判定标准。使用String 11.5网站对DEGs进行蛋白质相互作用分析,使用Cytoscape 3.8.0软件构建蛋白质相互作用网络图,筛选功能模块和关键基因。结果经筛选共获得25个DEGs,其中上调基因7个,下调基因18个。基因本体分析提示,DEGs在中性粒细胞激活、对细胞外刺激的反应、核受体辅助因子的活性、ATP酶活性、细胞-基质交界处、细胞-细胞交界处、细胞周期、内吞作用等方面富集。利用Cytoscape筛选出的关键基因分别是MMP9、IGF1、CHI3L1、CXCL10、CDKN1A、CCL20、IGFBP2、NRG1。结论通过生物信息学分析获得的8个NAFLD疾病相关特征差异表达关键基因,旨在为更深入研究NAFLD的发病机制及潜在治疗靶点提供方向。Objective To screen and analyze the characteristics of key differentially expressed genes(DEGs)in non-alcoholic fatty liver disease(NAFLD)with bioinformatics method,so as to provide new ideas for the prevention and treatment of NAFLD.Methods Two gene chips GSE48452 and GSE63067 were downloaded from Gene Expression Omnibus(GEO)database,DEGs were screened from healthy and NAFLD samples using GEO2R online analysis tool(P<0.05,|log_(2)FC|>0.5).R 4.1.Osoftware was used to screen out up-regulated DEGs,and the volcano map and heat map were made.Venn diagrams were made for common down-regulated DEGs.To understand the biological function and pathways of the DEGs,gene ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KECG)pathway analysis were performed using the DAVID online tool.P<0.05 was regarded as the cut-off criteria.String 11.5 website was used for protein-protein interaction(PPI)analysis of DEGs respectively,and Cytoscape 3.8.0 software was used to construct PPI network diagram and screen function modules and hub genes.Results A total of 25 DEGs were obtained by screening,including 7 up-regulated genes and 18down-regulated genes.GO analysis indicated that DEGs were enriched in neutrophil activation,response to extracellular stimulation,nuclear receptor cofactor activity,ATPase activity,cell-matrix junction,cell-cell junction,cell cycle,and endocytosis.The key genes screened by Cytoscape were MMP9,ICF1,CHI3LI,CXCL10,CDKN1A,CCL20,ICFBP2 and NRG1.Conclusion Eight DEGs related to NAFLD were identified by bioinformatics analysis,aiming to provide directions for further study of the pathogenesis and potential therapeutic targets of NAFLD.

关 键 词：非酒精性脂肪性肝病 非酒精性脂肪性肝炎 生物信息学分析 GEO数据库 

分 类 号：R575.1[医药卫生—消化系统]