生物信息学分析揭示主动脉瘤潜在的诊断标志物和发病机制

Bioinformatics analysis reveals potential diagnostic markers and pathogenesis of aortic aneurysms

目的确定主动脉瘤的潜在诊断和治疗基因。方法从Gene Expression Omnibus(GEO)数据库下载mRNA表达谱数据集,分为训练集和验证集。分析训练集数据以确定主动脉瘤和正常人的差异表达基因(differentially expressed genes,DEGs)。利用基因本体论(Gene Ontology,GO)和京都基因和基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)分析研究DEGs功能。利用机器学习和验证集数据筛选诊断标志物,并确定循环生物标志物。最后,通过免疫细胞浸润分析和单细胞测序分析确定所选诊断标志物的功能。结果在主动脉瘤和正常人间检测到2006个GEGs,其中807个上调,1199个下调。GO分析和KEGG通路分析显示,主动脉瘤中免疫反应相关信号显著富集。LASSO回归和验证集数据确定CXCL5、TGM3、BTC和ITGA10为潜在的诊断标志物,并有较好的诊断效能。最后,确定主动脉瘤中有多种免疫细胞浸润,并且巨噬细胞可能分泌CXCL5来影响中性粒细胞,从而参与主动脉瘤的病理过程。结论CXCL5、TGM3、BTC和ITGA10基因是主动脉瘤潜在的诊断标志物,巨噬细胞分泌的CXCL5可能是主动脉瘤的发病机制之一。

Objectives expression data were downloaded from the Gene Expression Omnibus(GEO)database,and set up as training set and validation set. Training set data were analyzed to identify differentially expressed genes(DEGs)in aortic aneurysms and normal humans. Then,Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis were used to investigate the functions of DEGs. Further,machine learning methods and validation set data were used to screen diagnostic markers and further identify circulating biomarkers. Finally,the function of selected diagnostic markers was determined by immune cell infiltration analysis and single-cell sequencing analysis.Results 2 006 GEGs(188 up-regulated and 1 011 down-regulated)were detected between aortic aneurysms and normal humans.GO and KEGG pathway analysis showed that immune response-related signals were significantly enriched in aortic aneurysms. LASSO model and validation set data identified CXCL5,TGM3,BTC and ITGA10 as potential diagnostic markers with good diagnostic performance. Finally,a variety of immune cells were identified in aortic aneurysms. It was found that macrophages may secrete CXCL5 to influence neutrophils,thereby participating in the pathology of aortic aneurysms.Conclusions CXCL5,TGM3,BTCand ITGA10 genes are potential diagnostic markers of aortic aneurysms,and CXCL5 secreted by macrophages may be one of the pathogenesis of aortic aneurysm.