摘要
目的利用生物信息学方法探究A型急性主动脉夹层(AAAD)的病理机制、关键靶点以及诊断生物标志物。方法GEO数据库下载GSE52093数据集,基于差异分析和WGCNA算法,构建基因共表达模块,对关键模块基因进行功能富集分析及PPI网络分析,探究关键模块基因参与AAAD的分子机制,并筛选出与AAAD密切相关的Hub基因。结果从GSE52093数据集中共鉴定出218个差异表达基因,其中上调基因135个,下调基因82个;另基于差异表达基因识别出4个基因模块,包括Turquoise模块(95个基因)、Blue模块(91个基因)、Yellow模块(20个基因)、Grey模块(11个基因),其中Turquoise模块与AAAD相关性最显著。关键基因模块在多种生物途径中富集,包括肌动蛋白细胞骨架的调节(regulation of actin cytoskeleton)、钙信号通路(calcium signaling pathway)、黏着斑途径(focal adhesion)、血管平滑肌收缩(vascular smooth muscle contraction)、心肌细胞中的肾上腺素能信号转导(adrenergic signaling in cardiomyocytes)、Wnt信号通路(Wnt signaling pathway)等。从PPI网络中筛选出10个与AAAD密切相关的Hub基因,分别为ACTC1、ACTN4、NEXN、MYOZ2、CSRP1、PPP1R12B、RYR2、MYL9、ACTG2、CASQ2,这些Hub基因在AAAD中均表达下调。结论本研究利用生物信息学方法筛选出与AAAD密切相关的生物途径和Hub基因,将为AAAD病理机制研究以及诊断生物标物和治疗靶点的发现提供基础。
Objective To explore the pathological mechanism,key targets and diagnostic biomarkers of type A acute aortic dissection(AAAD)by bioinformatics methods.Methods The GSE52093 dataset was downloaded from the GEO database.Based on the difference analysis and WGCNA algorithm,the gene co-expression module was constructed.The key module genes were subjected to functional enrichment analysis and PPI network analysis to explore the molecular mechanism of key module genes participating in AAAD,and Hub genes closely related to AAAD were screened.Results A total of 218 differentially expressed genes were identified from the GSE52093 dataset,including 135 up-regulated genes and 82 down-regulated genes.In addition,four gene modules were identified based on differentially expressed genes,including Turquoise module(95 genes),Blue module(91 genes),Yellow module(20 genes)and Grey module(11 genes),among which Turquoise module had the most significant correlation with AAAD.Key gene modules were enriched in multiple biological pathways,including regulation of actin cytoskeleton,calcium signaling pathway,focal adhesion pathway,vascular smooth muscle contraction,adrenergic signaling in cardiomyocytes,Wnt signaling pathway and so on.Ten Hub genes closely related to AAAD were screened from the PPI network,namely ACTC1,ACTN4,NEXN,MYOZ2,CSRP1,PPP1R12 B,RYR2,MYL9,ACTG2 and CASQ2,which were down-regulated in AAAD.Conclusion In this study,bioinformatics methods were used to screen out the biological pathways and Hub genes closely related to AAAD,which will provide a basis for the study of the pathological mechanism of AAAD and the discovery of diagnostic biomarkers and therapeutic targets.
作者
龚道星
GONG Dao-xing(Department of Vascular Surgery,Changsha First Hospital,Changsha 410000,Hunan,China)
出处
《医学信息》
2023年第7期9-16,共8页
Journal of Medical Information
