冠状动脉旁路移植术后心房颤动标志物的筛选与生物信息学分析
Screening and bioinformatic analysis of biomarkers of postoperative atrial fibrillation after coronary artery bypass grafting
彭媛媛 1魏宝柱 1李行2
作者信息
- 1. 430071 武汉,武汉大学中南医院心血管内科
- 2. 430071 武汉,武汉大学中南医院综合医疗科
- 折叠
摘要
目的 通过生物信息学方法探究行冠状动脉旁路移植术(CABG)术后心房颤动(POAF)患者心脏组织的差异表达基因及相关信号通路分析.方法 通过GEO数据库获取GSE62871和GSE143924基因芯片数据集,将两个数据集合且去除批次效应,筛选CABG后发生POAF的患者为POAF组,未发生POAF的患者为non-POAF组,利用R语言的limma包获得差异表达基因(DEGs);分别采用DAVID、Webgestalt及STRING分析平台对DEGs进行基因本体(GO)分析、京都基因与基因组百科全书(KEGG)分析及蛋白质相互作用网络(PPI)分析;根据PPI网络的度值(Degree)筛选出枢纽基因,对枢纽基因行皮尔森(Pearson)相关性分析及受试者工作特征分析(ROC分析),明确枢纽基因之间的相关性及对POAF的诊断价值.结果 研究共获得符合条件的DEGs 151个,相较于non-POAF组,POAF组中表达上调的基因有130个,表达下调的基因有21个.GO分析表明DEGs主要参与了蛋白质水解、细胞黏附、转运等通路.KEGG信号通路富集分析主要涉及细胞黏附分子、紧密连接、补体与凝血级联通路等通路.PPI分析筛选获得了5个枢纽基因,分别为CDH1、C1QA、BMP2、EGR1和TLR2,对枢纽基因行相关性分析发现C1QA与TLR2之间存在强烈的正相关关系,进行ROC分析发现C1QA和BMP2诊断POAF的价值较高.结论 基于GEO数据库的生物信息学分析,CABG后发生/未发生POAF的患者间存在多个DEGs,且DEGs参与了多条生物学通路,这些DEGs可能是潜在的重要研究及治疗靶点.
Abstract
Objective To explore the differentially expressed genes and related signaling pathways in the heart tissue of patients with postoperative atrial fibrillation(POAF)after coronary artery bypass grafting(CABG)by using bioinformatic methods.Methods The microarray gene datasets GSE62871 and GSE143924 were downloaded through the GEO database,combining two data sets and removing batch effects.Patients with POAF after CABG were set as the POAF group,and those without POAF were set as the non-POAF group,and differentially expressed genes were obtained by limma package based on R language.DAVID,Webgestalt and STRING platforms were respectively used to conduct gene ontology(GO),Kyoto encyclopedia of genes and genomes(KEGG)pathway and protein-protein interaction(PPI)network analysis for DEGs.The degree of the PPI network was used to screen out hub genes,and the Pearson correlation and Receiver operating characteristic(ROC)analysis of hub genes were performed,respectively,to determine the correlation and the diagnostic value of POAF among hub genes.Results A total of 151 DEGs were obtained.Compared with the non-POAF group,130 genes were up-regulated and 21 genes were down-regulated in the POAF group.GO analysis showed that DEGs were mainly involved in biological processes such as Proteolysis,Cell adhesion,and Transport.KEGG analysis showed that DEGs were mainly involved in pathways such as Cell adhesion molecules(CAMs),Tight junction,Complement and coagulation cascades and so on.5 hub genes were recognized by PPI analysis,including CDH1,C1QA,BMP2,EGR1 and TLR2.Pearson correlation analysis of hub genes found that there was a strong positive correlation between C1QA and TLR2,and ROC analysis found that C1QA and BMP2 were of high diagnostic value for POAF.Conclusion Bioinformatics analysis based on the GEO database showed that there are DEGs among patients with or without POAF after CABG.These DEGs are involved in multiple biological pathways and may be potential important targets for research and treatment.
关键词
冠状动脉旁路移植术/术后心房颤动/生物信息学/靶点Key words
Coronary artery bypass grafting/Postoperative atrial fibrillation/Bioinformatics/Targets引用本文复制引用
基金项目
湖北省自然科学基金青年基金(2023AFB693)
出版年
2024