宁夏医科大学学报2024,Vol.46Issue(2) :130-136.DOI:10.16050/j.cnki.issn1674-6309.2024.02.004

下肢外周动脉疾病铁死亡相关基因的生物信息学分析

Bioinformatics Analysis of Ferroptosis-related Genes in Peripheral Artery Disease of Lower Extremities

金学连 何霄 贾海博 吴丹 赵凯
宁夏医科大学学报2024,Vol.46Issue(2) :130-136.DOI:10.16050/j.cnki.issn1674-6309.2024.02.004

下肢外周动脉疾病铁死亡相关基因的生物信息学分析

Bioinformatics Analysis of Ferroptosis-related Genes in Peripheral Artery Disease of Lower Extremities

金学连 1何霄 1贾海博 1吴丹 1赵凯2
扫码查看

作者信息

  • 1. 宁夏医科大学中医学院,银川 750004;宁夏区域高发病中西医结合防治研究重点实验室,银川 750004
  • 2. 宁夏医科大学中医学院,银川 750004;宁夏区域高发病中西医结合防治研究重点实验室,银川 750004;宁夏医科大学总医院,宁夏医科大学第一临床医学院,银川 750004
  • 折叠

摘要

目的 探索下肢外周动脉疾病的潜在铁死亡相关生物标志物及诊断治疗靶点.方法 应用生物信息学方法从基因表达综合数据库(gene expression omnibus,GEO)中下载下肢外周动脉疾病的转录组数据集,筛选出差异表达基因(differential expressed genes,DEGs),并与铁死亡基因取交集,得到下肢外周动脉疾病相关的铁死亡基因,对其进行功能富集,同时通过受试者工作特征(receiver operating characteristic,ROC)曲线分析下肢外周动脉疾病相关的铁死亡基因的诊断价值;之后构建蛋白质相互作用网络,应用Cytoscape中的算法预测关键基因;最后通过miRWalk预测靶向关键基因的miRNA并构建网络图.结果 共筛选出 9 个下肢外周动脉疾病铁死亡相关基因,GO与KEGG的功能富集分析结果表明,这些基因与铁死亡、免疫调节、凋亡及糖尿病、动脉粥样硬化等相关,ROC诊断提示下肢外周动脉疾病患者中 9 个相关的铁死亡基因的平均曲线下面积(area under the curve,AUC)为 0.930;基于算法筛选出 4 个关键基因:HMOX1、ALOX5、IL1B和CY BB,而CY BB和HMOX1 同时受miR-6734-3p调控.结论 通过生物信息学方法分析得出HMOX1、ALOX5、IL1B和CY BB在下肢外周动脉疾病中存在诱导铁死亡的潜在作用,而miR-6734-3p作为HMOX1 与CY BB的共同靶向miRNA,有望成为潜在诊断生物标志物及治疗靶点.

Abstract

Objective To explore potential ferroptosis related biomarkers and diagnostic and therapeutic targets in peripheral artery disease(PAD)of lower extremities.Methods Transcriptome data set of PAD of lower limbs were downloaded from gene expression omnibus(GEO),and differential expressed genes(DEGs)were screened using R language,and their intersection with ferroptosis genes was selected.Ferroptosis related differential genes related to lower limb PAD were obtained,and gene ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)functional enrichment analysis of ferroptosis related differential genes were conducted.The diagnostic value of ferroptosis related differential genes was analyzed by receiver operating characteristic(ROC).Then the protein interaction network was constructed,and the algorithm in Cytoscape was applied to predict key genes.Finally,miRNA targeting key genes were predicted by miRWalk,and the network map was constructed.Results A total of 9 genes related to ferroptosis in PAD lower limbs were screened,and the functional abundance analysis results of GO and KEGG showed that they were related to ferroptosis,immune regulation,apoptosis,diabetes,atherosclerosis,etc.ROC diagnosis suggested that the average area under the curve(AUC)of 9 ferroptosis related differential genes in PAD patients is 0.930.Four key genes were selected based on the algorithm:HMOX1,ALOX5,IL1B and CY BB,while CY BB and HMOX1 were regulated by miR-6734-3p.Conclusion The bioinformatics analysis showed that HMOX1,ALOX5,IL-1B and CY BB have potential roles in inducing ferroptosis in lower limbs PAD,and miR-6734-3p,as a co-targeting miRNA of HMOX1 and CY BB,is expected to become a potential diagnostic biomarker and therapeutic target.

关键词

GEO数据库/下肢外周动脉疾病/铁死亡

Key words

GEO database/peripheral artery disease of lower extremity/ferroptosis

引用本文复制引用

基金项目

中国中医科学院中医基础理论研究所合作单位个人项目(YZ-202129)

出版年

2024
宁夏医科大学学报
宁夏医科大学

宁夏医科大学学报

CSTPCD
影响因子:0.84
ISSN:1674-6309
参考文献量29
段落导航相关论文