Identification and validation of m7G-related genes related to macrophage immunity in acute myocardial infarction through comprehensive bioinformatics analysis

Acute myocardial infarction (AMI) is a fatal disease related to immune cell activation; however, the pathological molecular mechanisms associated with AMI and immunity remain unclear. This study aims to explore m7G-related hub genes associated with immune cell characteristics in AMI through the bioinformatics method.

Transcriptome sequencing data downloaded from GSE59867 (GPL6244) were used to screen m7G-related differentially expressed genes (DEGs) between AMI and non-AMI controls. Abnormal immune cell characteristics was analyzed by single-sample gene set enrichment analysis (ssGSEA) algorithm. Hub genes were screened from m7G-related DEGs by the support vector machine recursive feature elimination (SVM-RFE) algorithm and random forest tree model. The association of hub genes with immune cell types was analyzed by GSEA and Spearman correlation analysis. A mouse AMI model and hypoxia-stimulated macrophage model were established to verified the function of CYFIP1 on macropahges.

We identified significant differences in 21 types of immune cells and 13 m7G-related DEGs between AMI and non-AMI controls. m7G-related DEGs were enriched in nucleoside nuclear catabolism, RNA modification and translation regulation, the HIF-1 signaling pathway, etc. 111 AMI samples were divided into three clusters based on the cluster analysis of m7G-related DEG expression profiles, and immune cell types were significantly different in the three clusters. Four hub genes including CYFIP1, EIF4E2, IFIT5, and NCBP3 were screened and positively or negatively correlated with AMI. ROC curve verified the efficiency of the 4 hub genes in the diagnosis prediction models of AMI. CYFIP1 had the best prediction efficiency of than other 3 hub genes. GESA enrichment and Spearman correlation analysis found that hub genes were associated with inflammation and immune, especially CYFIP1 had a strong statistical relationship with macrophages, Monocyte, etc. By experiments, we found that CYFIP1 was upregulated in AMI patients and animal models, and knockdown of CYFIP1 inhibited hypoxia-mediated macrophage inflammatory response.

m7G-related hub genes are associated with immune cell characteristics in AMI, among which CYFIP1 may play a key role in the regulatory network of macrophage immune response.