目的 利用生物信息学方法筛选急性心肌梗死(acute myocardial infarction,AMI)潜在生物标志物,为其免疫病理机制研究及辅助诊断提供理论依据.方法 从基因表达综合数据库(Gene Expression Omnibus,GEO)下载AMI患者数据集GSE66360,获取基因表达数据,利用加权基因共表达网络分析(weighted gene co-expression network a-nalysis,WGCNA)构建基因共表达网络,选择与AMI发生发展高度正相关的模块,提取模块基因,同时对表达数据进行差异基因分析,两者关联获得AMI高度相关差异表达基因并对其进行生物学功能和信号通路富集分析.进一步利用最小绝对值收敛和选择算子算法(least absolute shrinkage and selection operator,LASSO)回归模型筛选核心基因,验证核心基因表达水平并绘制受试者工作特征(receiver operating characteristic,ROC)曲线验证模型准确性.通过基因集富集分析(gene set enrichment analysis,GSEA)探讨核心基因富集的信号通路,利用ImmuCellAI进行免疫细胞浸润分析,探讨高水平浸润免疫细胞与核心基因表达的相关性.结果 筛选获得28个AMI高度相关差异表达基因,富集分析显示,其与免疫应答、免疫细胞激活等生物过程有关,并参与补体和凝血级联反应、流体剪切应力与动脉粥样硬化等信号通路.LASSO回归模型识别出IL1R2、IRAK3、NFIL3、THBD、JDP2为AMI核心基因,其相互作用紧密,并在AMI样本中均显著高表达(P＜0.001),单个核心基因ROC曲线的曲线下面积(area under the curve,AUC)均≥0.880,综合AUC为0.952,对AMI具有诊断价值.核心基因主要富集于丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)信号通路、趋化因子信号通路和感染免疫相关信号通路.AMI样本中存在多种免疫细胞差异浸润,其中树突状细胞、巨噬细胞、中性粒细胞和自然调节性T细胞在AMI样本中高水平浸润(P＜0.05),且核心基因表达水平均与巨噬细胞、中性粒细胞浸润呈正相关关系,与自然调节性T细胞无关.结论 免疫代谢相关途径在AMI疾病进程中发挥重要作用,IL1R2、IRAK3、NFIL3、THBD和JDP2可能作为AMI患者中与免疫相关的特征基因和潜在的生物标志物,辅助AMI早期诊疗.
Screening Potential Biomarkers and Exploring Immunological Characteristics of Acute Myocardial Infarction
Objective To screen potential biomarkers of acute myocardial infarction(AMI)with bioinformatics methods,and provid theoretical support for the study of its immunopathological mechanisms and auxiliary diagnosis.Methods AMI patient dataset GSE66360 was downloaded from the Gene Expression Omnibus database(GEO)to obtain gene expression data.A weighted gene co-expression network analysis(WGCNA)was used to construct a gene co-ex-pression network,selecting modules highly positively correlated with the occurrence and development of AMI.Module genes were extracted,and differential gene expression analysis was performed on the expression data.Highly correlated differentially expressed genes related to AMI were identified and subjected to biological function and signaling pathway en-richment analysis.Further,core genes were screened using the least absolute shrinkage and selection operator(LASSO)regression model.Core gene expression levels were validated,and receiver operating characteristic(ROC)curves were plotted to verify the model's accuracy.Gene set enrichment analysis(GSEA)was employed to explore the signaling path-ways of core genes enrichment,and ImmuCellAI was used to analyze immune cell infiltration,investigating the correlation between high-level infiltrating immune cells and core gene expression.Results Twenty-eight differ-entially expressed genes with highly correlation with AMI were identified,which were related to biological processes such as immune response and immune cell activation.These genes participated in signaling pathways such as complement and coagulation cascades,fluid shear stress and atherosclero-sis.The LASSO regression model identified five core genes for AMI:interleukin 1 receptor type 2(IL-1R2),interleukin 1 receptor associated kinase 3(IRAK3),interleukin 3 regulated(NFIL3),thrombomodulin(THBD)and jun dimeriza-tion protein 2(JDP2).These core genes exhibited tight interactions and were significantly over expressed in AMI samples(P＜0.001),the area under the curve(AUC)of single core gene's ROC curve was ≥0.880,and a combined AUC was 0.952,which was diagnostic value for AMI.Core genes were primarily enriched in the mitogen-activated protein kinase(MAPK)signaling pathway,chemokine signaling pathway,and infection and immunity-related signaling pathways.There were various immune cells exhibited differential infiltration in AMI samples,and dendritic cells,macrophages,neutrophils,and natural regulatory T cells were infiltration at high levels in AMI samples(P＜0.05).Core gene expres-sion levels were positively correlated with macrophage and neutrophil infiltration,but not with natural regulatory T cells.Conclusion Immune metabolic pathways play a significant role in the progression of AMI.IL1R2,IRAK3,NFIL3,TH-BD,and JDP2 may serve as immune-related characteristic genes and potential biomarkers in AMI patients,aiding in early diagnosis and treatment of AMI.
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