Identification of Potential Biomarkers Associated with Acute Myocardial Infarction by Weighted Gene Coexpression Network Analysis

Abstract

Background. In the general population, acute myocardial infarction (AMI) represents a significant cause of mortality. This study is aimed at identifying novel diagnostic biomarkers to aid in treating and diagnosing AMI. Methods. The Gene Expression Omnibus (GEO) database was explored to extract two microarray datasets, GSE66360 and GSE48060, which were subsequently merged into a single cohort. Both AMI and control samples were analyzed for differentially expressed genes (DEGs), which were subsequently subjected to weighed gene coexpression network analysis (WGCNA) to identify the most significant module. Gene Ontology (GO) and pathway analyses subsequently carried out the most significant gene modules along with construction of a protein-protein interaction network (PPI). Cytoscape plugin cytoHubba allowed for the prediction of the top 4 key genes according to the network maximal clique centrality (MCC) algorithm. The expression levels and diagnostic value of the four key genes were additionally verified in the GSE62646 dataset. Results. A WCGNA analysis revealed 878 DEGs which were clustered into 6 modules. The module with the most significance in AMI was colored blue. Subsequent GO and KEGG pathway enrichment analysis on blue module genes revealed that they were primarily enriched in the inflammation-related pathways. These findings, in combination with PPI and coexpression networks, resulted in the identification of the top four genes by cytoHubba, which included leukocyte immunoglobulin-like receptor B2 (LILRB2), toll-like receptor 2 (TLR2), neutrophil cytosolic factor 2 (NCF2), and S100A9. Among them, LILRB2, NCF2, and S100A9 were validated in the GSE62646 dataset. Conclusions. The results suggested that LILRB2, NCF2, and S100A9 could be potential gene biomarkers for AMI.