Bioinformatics-based analysis of key genes associated with endoplasmic reticulum stress in myocardial infarction

Abstract

Abstract Background Endoplasmic reticulum stress (ERS) is a critical pathological factor that drives myocardial infarction (MI) progression. This study aimed to screen and validate core ERS-related hub genes involved in acute myocardial infarction (AMI) pathogenesis by integrating bioinformatics analysis and in vivo experimentation. Methods Two AMI-related transcriptome datasets (GSE97320, GSE48060) were retrieved from the Gene Expression Omnibus (GEO) database. After data integration and batch effect correction, differentially expressed genes (DEGs) between AMI patients and healthy controls were screened and visualized. ERS-associated genes were downloaded from the Molecular Signatures Database (MSigDB), and overlapping genes between DEGs and ERS-related genes were defined as ERS-related genes (ERSRGs) for subsequent analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to explore the functional characteristics and signaling mechanisms of ERSRGs. Core hub genes were identified by combining protein-protein interaction (PPI) network analysis and random forest (RF) algorithm. The external GEO dataset GSE66360 was used to verify the expression and diagnostic value of candidate hub genes. An AMI mouse model was established, and quantitative real-time polymerase chain reaction (qPCR) was adopted to detect hub gene mRNA levels in myocardial tissues for in vivo validation. Results A total of 633 DEGs and 267 ERS-related genes were screened, among which 15 overlapping ERSRGs were obtained. Combining PPI network topological analysis and RF feature screening, CEBPB and PPP1R15A were identified as core hub genes. External dataset validation confirmed their significant upregulation in AMI samples with good diagnostic efficacy. In vivo qPCR results further verified that the mRNA expression of CEBPB and PPP1R15A was significantly elevated in myocardial tissues of AMI model mice compared with the sham group ( P < 0.05). Conclusion CEBPB and PPP1R15A are key ERS-related hub genes with upregulated expression in AMI. They exert crucial regulatory effects on MI pathological processes and have high research potential for exploring the molecular mechanism of myocardial ischemic injury.