Screening Potential Biomarkers and Exploring Immunological Characteristics of Acute Myocardial Infarction

CAO Shuqing; CHEN Meng; ZHANG Yujing; GUO Chenjie; HU Peiting; JIAO Boheng; ZHANG Yuanyuan

doi:10.13730/j.issn.2097-2148.2024.11.009

Abstract：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.