基于GEO数据库芯片的致心律失常性右室心肌病关键基因筛选与生物信息学分析

Identification of key genes in arrhythmogenic right ventricular cardiomyopathy based on a GEO database chip: a bioinformatics analysis

目的:寻找致心律失常性右室心肌病(ARVC)发病关键基因。方法:从GEO数据库获得人类ARVC现有信息芯片,筛选出ARVC心肌和正常心肌间差异基因。通过David数据库进行基因本体论(GO)功能注释和京都基因与基因组百科全书(KEGG)通路分析,利用String数据库和Cytoscape软件构建蛋白质相互作用(PPI)网络。结果:共鉴定出101个差异基因,包括40个上调基因和61个下调基因。GO分析显示,P<0.01且基因数>10的生物过程(BP)包括炎症反应和信号转导,细胞组分(CC)包括细胞膜、细胞外空间和细胞外区域。KEGG分析显示,P<0.01的通路为肿瘤坏死因子(TNF)信号通路。经过PPI分析筛选得出10个关键基因:白细胞介素6(IL-6)、CCL2、AIF1、CD14、CCR1、FCER1G、FPR1、PTGS2、S100A9和S100A8。结论:ARVC的发生发展可能与炎症机制密切相关,可作为潜在的治疗靶点为ARVC进一步研究提供依据。

Objective:To search for the key genes that cause arrhythmogenic right ventricular cardiomyopathy(ARVC).Method:The existing information chip of human ARVC was obtained from the GEO database,and the differential genes between normal cardiac tissues and ARVC cardiac tissues were screened out.Functional annotation of gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)were conducted through David database,and protein-protein interaction(PPI)network was constructed by using String database and Cytoscape software.Result:A total of 101 differential genes were identified,including 40 up-regulated genes and 61 down-regulated genes.GO analysis showed that the biological process(BP)with P<0.01 and gene number>10 includes inflammatory response and signal transduction.The cell component(CC)included cell membrane extracellular space and extracellular region.KEGG analysis showed that the pathway with P<0.01 was the TNF signaling pathway.After PPI analysis,10 key genes were identified:IL-6,CCL2,AIF1,CD14,CCR1,FCER1 G,FPR1,PTGS2,S100 A9 and S100 A8.Conclusion:The occurrence and development of ARVC may be closely related to the mechanism of inflammation,which can be used as a potential therapeutic target to provide a basis for further research of ARVC.