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CYBB,而CYBB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CYBB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CYBB的共同靶向miRNA,有望成为潜在诊断生物标志物及治疗靶点。
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 CYBB,while CYBB and HMOX1 were regulated by miR-6734-3p.Conclusion The bioinformatics analysis showed that HMOX1,ALOX5,IL-1B and CYBB have potential roles in inducing ferroptosis in lower limbs PAD,and miR-6734-3p,as a co-targeting miRNA of HMOX1 and CYBB,is expected to become a potential diagnostic biomarker and therapeutic target.
作者
金学连
何霄
贾海博
吴丹
赵凯
JIN Xuelian;HE Xiao;JIA Haibo;WU Dan;ZHAO Kai(School of Traditional Chinese Medicine,Ningxia Medical University,Yinchuan 750004,China;Ningxia Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of High Incidence,Yinchuan 750004,China;General Hospital of Ningxia Medical University,First Clinical Medical College of Ningxia Medical University,Yinchuan 750004,China)
出处
《宁夏医科大学学报》
2024年第2期130-136,共7页
Journal of Ningxia Medical University
基金
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)。
关键词
GEO数据库
下肢外周动脉疾病
铁死亡
GEO database
peripheral artery disease of lower extremity
ferroptosis
