摘要
目的通过生物信息学的方法探讨腹主动脉瘤(AAA)性别相关的基因表达差异并筛选关键基因。方法从基因表达数据库(GEO)下载GSE7084、GSE197748与GSE57691数据集, 对GSE7084、GSE197748数据集中的样本根据不同性别进行差异分析。对男性AAA特有差异基因(msDEG)及共有差异基因(cDEG)构建蛋白质-蛋白质相互作用网络(PPI)。使用Metascape数据库对交集基因进行基因本体(GO)富集分析以及京都基因和基因组百科全书(KEGG)富集分析。使用CIBERSORT算法及mMCPcounter进行免疫浸润评估。使用最小绝对收缩和选择算子(LASSO)以及随机森林(RF)算法筛选cDEG中的关键基因并在GSE7084数据集和GSE57691数据集中使用受试者工作特征(ROC)曲线评价关键基因对AAA的诊断效能。最后通过DGIdb数据库检索与关键基因互作的药物。结果共获取112个msDEG及42个cDEG, 富集分析表明msDEG主要富集于炎性相关通路及与髓系细胞相关的免疫相关通路, 主要由转录因子RELA和NFKB1调控, 而cDEG主要富集于平滑肌细胞功能相关通路, 受转录因子KLF5和ETS1调控。男性AAA组中单核细胞免疫浸润分数高于女性AAA组(0.138±0.031比0.018±0.013, t=-4.581, P<0.05)。通过筛选cDEG得到2个关键基因, 分别是白细胞介素2受体γ链(IL2RG)和含富含亮氨酸的重复序列的G蛋白耦联受体6(LGR6), 在GSE7084数据集中, 2个基因诊断AAA的曲线下面积(AUC)分别为1、1;在GSE7084数据集中AUC分别为0.92、0.91。通过DGIdb数据库得到13个潜在的靶向药物。结论核因子-κB介导的炎性反应及髓系细胞相关的免疫反应在男性AAA中更为显著。
ObjectiveInvestigating sex-related gene expression differences in abdominal aortic aneurysm(AAA)through bioinformatics methods and identifying key genes.MethodsDatasets GSE7084,GSE197748,and GSE57691 were downloaded from the Gene Expression Omnibus(GEO)database.Differential analysis was performed on the samples in the GSE7084 and GSE197748 datasets based on sex.A protein-protein interaction(PPI)network was constructed for male-specific differentially expressed genes(msDEGs)and common differentially expressed genes(cDEGs).Metascape was used to conduct Gene Ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis for intersecting genes.Immune infiltration was assessed using the CIBERSORT algorithm and mMCPcounter.Key genes from the cDEGs were selected using the least absolute shrinkage and selection operator(LASSO)and random forest(RF)algorithms,and the diagnostic performance of the key genes for AAA was evaluated using receiver operating characteristic(ROC)curves in the GSE7084 and GSE57691 datasets.Finally,drugs interacting with the key genes were identified using the DGIdb database.ResultsIn this study,a total of 112 msDEGs and 42 cDEGs were obtained.Enrichment analysis indicated that msDEGs were primarily enriched in inflammation-related pathways and immune-related pathways associated with myeloid cells,mainly regulated by the transcription factors RELA and NFKB1.In contrast,cDEGs were primarily enriched in pathways related to smooth muscle cell function,regulated by the transcription factors KLF5 and ETS1.The monocyte immune infiltration score in the male AAA group was higher than in the female AAA group(0.138±0.031 vs.0.018±0.013,t=-4.581,P<0.05).By screening cDEGs,we identified two key genes:interleukin-2 receptor gamma chain(IL2RG)and leucine-rich repeat-containing G-protein coupled receptor 6(LGR6).In the GSE7084 dataset,the area under the curve(AUC)for diagnosing AAA with these two genes was 1 and 1,respectively;in the GSE7084 dataset,the AUCs were 0.92 and 0.91,respectively.Through the DGIdb database,13 potential targeting drugs were identified.ConclusionNuclear factor-κB(NF-κB)-mediated inflammatory response and myeloid cell-related immune response are more pronounced in male AAA.
作者
刘仕睿
焦周阳
单金涛
夏磊
化召辉
李震
程帅
Liu Shirui;Jiao Zhouyang;Shan Jintao;Xia Lei;Hua Zhaohui;Li Zhen;Cheng Shuai(Department of Endovascular Surgery,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China)
出处
《中华实验外科杂志》
2024年第12期2752-2755,共4页
Chinese Journal of Experimental Surgery
