冠状动脉疾病差异基因富集和加权基因共表达网络分析  

Analysis of differential gene enrichment and weighted gene co-expression network in coronary artery disease

作　　者：朱宝华 孙岩 ZHU Baohua;SUN Yan(Department of General Practice,Ji′nan City People′s Hospital of Shandong Province,Ji′nan,Shandong,271100;Department of Vascular Surgery,Provincial Hospital Affiliated to Shandong First Medical University,Ji′nan,Shandong,250021)

机构地区：[1]山东省济南市人民医院全科医学科,山东济南271100 [2]山东第一医科大学附属省立医院血管外科,山东济南250021

出　　处：《实用临床医药杂志》2021年第17期15-21,共7页Journal of Clinical Medicine in Practice

基　　金：山东省中医药科技发展计划项目(2019-0303);山东省医药卫生科技发展计划项目(2018WS273)。

摘　　要：目的采用基因集富集分析和加权基因共表达网络分析探讨冠状动脉疾病的差异表达基因,挖掘与冠状动脉疾病发病相关的关键基因。方法从美国国家生物技术信息中心(NCBI)基因表达综合数据库下载GSE71226数据集,筛选冠状动脉疾病差异基因并进行富集分析;对差异基因进行基因集富集分析,筛选冠状动脉疾病差异表达基因相关的微小RNA(miRNAs)并构建调控网络;根据基因的相关性,构建基因共表达模块,并计算模块基因与临床信息的相关性;选取与临床表型显著相关的模块,构建蛋白质互作网络并筛选核心基因。结果经筛选,共获取冠状动脉疾病差异表达基因130个,富集于Hippo、流体剪切力与动脉粥样硬化、一磷酸腺苷依赖的蛋白激酶(AMPK)、Wnt、核苷酸结合寡聚化结构域(NOD)样受体和白细胞介素17等信号通路上。富集分析显示,miR-503-3p、miR-3674、miR-5088-5p、miR-4486等miRNAs与冠状动脉疾病关系密切。根据基因表达的相关性,获取10个共表达模块,其中洋红色模块与冠状动脉疾病发病显著相关。经拓扑分析,BMP4和C3在网络中处于核心地位。结论冠状动脉疾病发病过程中基因表达存在显著差异,其病理过程涉及多靶点、多通路,可能受到多个miRNAs调控。BMP4和C3可能是冠状动脉疾病发病的关键基因。Objective To explore the differential expression genes of coronary artery disease by gene set enrichment analysis and weighted gene co-expression network analysis and excavate key genes associated with the development of coronary artery disease.Methods The GSE71226 dataset was downloaded from the Gene Expression Omnibus database of the National Center for Biotechnology Information(NCBI),and the differential genes of coronary artery disease were screened and the enrichment analysis was performed.The gene set enrichment analysis was performed on the differential genes to screen for microRNAs(miRNAs)associated with differential expression genes in coronary artery disease,and the regulation network was constructed.The gene co-expression modules were constructed based on the correlation of genes,and the correlation between gene modules and clinical information was calculated.The genes of modules significantly correlating with clinical phenotypes were selected to construct protein-protein interaction network for screening of the core genes.Results After screening,a total of 130 differential expression genes in coronary artery disease were obtained,enriched in signaling pathways such as Hippo,fluid shear stress and atherosclerosis,adenosine monophosphate-dependent protein kinase(AMPK),Wnt,nucleotide-binding oligomerization domain(NOD)like receptors and interleukin 17.Enrichment analysis showed that the miRNAs such as miR-503-3p,miR-3674,miR-5088-5p and miR-4486 were closely related to coronary artery disease.Based on the correlation of gene expression,10 co-expression modules were obtained,and the magenta module was significantly associated with the development of coronary artery disease.Topological analysis showed that BMP4 and C3 were the core genes of the protein-protein interaction network.Conclusion There are significant differences in gene expressions during the pathogenesis of coronary artery disease,the pathological process involves multiple targets and pathways,and pathogenesis involving in multiple targets and

关 键 词：冠状动脉疾病 信号通路 富集分析 蛋白质互作网络 流体剪切力 动脉粥样硬化 骨形态发生蛋白 

分 类 号：R541.4[医药卫生—心血管疾病] R543.3[医药卫生—内科学]