小儿特发性扩张型心肌病核心基因鉴定和免疫浸润分析  

Identification of Key Genes and Analysis of Immune Infiltration in Pediatric Idiopathic Dilated Cardiomyopathy

作　　者：尤红俊 赵倩倩 苟棋玲 董梦雅 YOU Hongjun;ZHAO Qianqian;GOU Qiling;DONG Mengya(Shaanxi Provincial People's Hospital,Xi'an 710068,Shaanxi,China)

机构地区：[1]陕西省人民医院,西安710068 [2]中国人民解放军空军军医大学第一附属医院

出　　处：《中西医结合心脑血管病杂志》2023年第20期3703-3710,共8页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

摘　　要：目的:利用生物信息学分析筛选小儿特发性扩张型心肌病(PIDC)的核心基因,并进行免疫浸润分析。方法:使用R语言对来自基因表达综合数据库(GEO)的PIDC转录谱进行差异分析。利用R语言对差异表达基因(DEGs)进行基因本体(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路富集分析。通过STRING数据库和CytoHubba构建蛋白-蛋白互作(PPI)网络及鉴定核心基因。利用比较毒理基因组学数据库(CTD)分析核心基因与心肌病、心力衰竭风险的关系。利用单样本基因集富集分析(ssGSEA)计算PIDC中28种免疫细胞在免疫浸润微环境中的比例。结果:PIDC左心室有137个DEGs,主要参与对外部刺激的正向调节、炎症反应的调节、中性粒细胞的激活和介导的免疫、细胞-基质黏附的正向调节、细胞外结构、含胶原的细胞外基质等。DEGs参与细胞凋亡、胰岛素抵抗、花生四烯酸代谢和缺氧诱导因子1(HIF-1)信号通路等。鉴定的核心基因为信号转导和转录激活因子3(STAT3)、CD68、高亲和力IgE受体γ亚基基因(FCER1G)、细胞周期素D1(CCND1)和CD163,其与心肌病、心力衰竭关联紧密。PIDC左心室组织中央记忆型CD_(8)^(+)T细胞的含量较高;活化的树突样细胞、骨髓来源的抑制性细胞、自然杀伤T细胞、浆细胞样树突状细胞、滤泡辅助性T细胞的含量较低。结论:炎症及免疫反应在PIDC的发病机制中发挥着重要作用,5个核心基因和6种免疫细胞与PIDC发生发展密切相关。Objective:To screen key genes of pediatric idiopathic dilated cardiomyopathy(PIDC)using bioinformatics analysis and perform analysis of immune infiltration.Methods:Differential analysis of PIDC transcriptional profiles from Gene Expression Omnibus(GEO)was performed using the R language.Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis of differentially expressed genes(DEGs)were conducted by R language.The STRING database and CytoHubba were used to construct the protein-protein interaction(PPI)network and identify the key genes.The association between key genes and risk of cardiomyopathy and heart failure was analyzed using the comparative toxicogenomics database(CTD).Single sample gene set enrichment analysis(ssGSEA)was used to calculate the proportion of 28 kinds of immune cells in immunoinfiltrated microenvironment with PIDC.Results:There were 137 DEGs in the left ventricular tissue of PIDC,which were mainly involved in the positive regulation of external stimuli,the regulation of inflammatory response,the activation and mediated immunity of neutrophils,the positive regulation of cell-matrix adhesion,the extracellular structure,and the extracellular matrix containing collagen.DEGs were involved in apoptosis,insulin resistance,arachidonic acid metabolism,and hypoxia-inducible factor-1(HIF-1)signaling pathway.The identified key genes were signal transducer and activitor of transcription 3(STAT3),CD68,high-affinity IgE receptor gamma subunit gene(FCER1G),cyclinD1(CCND1),and CD163,which were closely associated with cardiomyopathy and heart failure.The content of central memory CD_(8)^(+)T cell was increased in the left ventricular tissue of PIDC,while the contents of activated dendritic cell,myeloid-derived suppressor cell,natural killer T cell,plasmacytoid dendritic cell,and follicular helper T cells were decreased.Conclusion:Inflammation and immune response played an important role in the pathogenesis of PIDC.Five key genes and six kinds o

关 键 词：扩张型心肌病 差异表达基因 生物信息学 核心基因 免疫浸润 

分 类 号：R725.4[医药卫生—儿科]