肥厚型心肌病关键基因的鉴定及铁死亡机制  

Identification of hub genes related to hypertrophic cardiomyopathy and analysis of ferroptosis mechanism

作　　者：巴文强 李艳 李梦媛[3] BA Wen-qiang;LI Yan;LI Meng-yuan(Department of Pharmacy,Central People’s Hospital of Ji'an,Ji'an 343000,China;Department of Psychiatry,Ji'an Third People’s Hospital,Ji'an 343000,China;Department of Pharmacy,The Second Affiliated Hospital of Nanjing Medical University,Nanjing 210011,China)

机构地区：[1]吉安市中心人民医院药剂科,江西吉安343000 [2]吉安市第三人民医院心理科,江西吉安343000 [3]南京医科大学第二附属医院药学部,江苏南京210011

出　　处：《吉林医学》2023年第12期3351-3357,共7页Jilin Medical Journal

基　　金：江西省卫健委科技计划项目[项目编号:SKJP220228843];吉安市科技计划项目[项目编号:20222-026804]。

摘　　要：目的:利用生物信息学方法探究肥厚型心肌病(HCM)的关键基因、铁死亡基因和相关富集通路。方法:从GEO数据库下载GSE36961和GSE32453数据集,筛选共同差异表达基因(DEGs)进行富集分析,构建蛋白质相互作用(PPI)网络并鉴定关键基因,用GSE1145数据集验证关键基因的表达,绘制关键基因的受试者工作特征(ROC)曲线。此外,检索Genecards和FerrDb数据库,获得调控铁死亡基因并进行分析。结果:共筛选出136个共同DEGs,富集分析显示共同DEGs与流体剪切应力和动脉粥样硬化、糖尿病并发症中的晚期糖基化终产物及其受体信号通路等相关。PPI网络鉴定出4个关键基因,其中CCL2、CEBPD和PIM1在HCM中表达下调(均P<0.05),且对HCM有较高的诊断效能。另外,筛选出ATF3、LPCAT3和PIM1等10个调控铁死亡抗HCM的可能作用靶标,介导流体剪切应力和动脉粥样硬化、铁死亡等信号通路调控铁死亡途径。结论:CCL2、CEBPD和PIM1基因在HCM发病中具有重要作用,为HCM的诊断和治疗提供了参考,铁死亡相关基因为HCM发病机制的探索提供了新的方向。Objective To explore the hub genes,ferroptosis related genes and related enrichment pathways of hypertrophic cardio-myopathy(HCM)by bioinformatics methods.Method The GSE36961 and GSE32453 datasets were downloaded from the Gene Ex-pression Omnibus(GEO)database,the common differentially expressed genes(DEGs)were screened out and enrichment analysis was performed.Then,a protein-protein interaction(PPI)network of the common DEGs was established and to screen hub genes.The GSE1145 dataset was used to verify the expression of hub genes,and ROC curves of hub genes were drawn to identify.Genecards and FerrDb database were searched to obtain and analyze the genes regulating ferroptosis.Results The results of enrichment analysis of 136 common DEGs suggest that the common DEGs were related to fluid shear stress and atherosclerosis and advanced glycosylation end products-receptor of advanced glycosylation end products signaling pathway in diabetic complications et al.After constructing of PPI network,the four hub genes were identified,among which CCL2,CEBPD and PIM1 are lowly expressed in HCM(all P<0.05),and had highly diagnostic efficiency for HCM.In addition,ten possible targets regulating ferroptosis and anti-HCM disease were selected,including ATF3,LPCAT3 and PIM1 et al.Ferroptosis pathway is regulated by mediating fluid shear stress and atherosclerosis and fer-roptosis signaling pathways.Conclusion The CCL2,CEBPD and PIM1 genes play an important role in the pathogenesis of HCM,pro-viding a reference for the diagnosis and treatment of HCM.Ferroptosis related genes could provide us with a novel direction for explora-tion of the pathogenesis of HCM.

关 键 词：肥厚型心肌病 关键基因 铁死亡 生物信息学 

分 类 号：R542.2[医药卫生—心血管疾病]