Identification of important genes related to ferroptosis and hypoxia in acute myocardial infarction based on WGCNA

Abstract

ABSTRACT Acute myocardial infarction (AMI) tends to cause severe heart failure and the population suffering from AMI gradually become younger. This study aims to determine the key genes associated with AMI, ferroptosis and hypoxia that could serve as novel biomarkers for AMI. There were 522 up-regulated genes and 119 down-regulated genes in GSE4648. Based on the expression of ferroptosis-related genes (FRGs) and hypoxia-related genes, the ferroptosis Z-score and the hypoxia Z-score calculated by ssGSEA were significantly higher in the infarcted area of AMI mice than in the control group, and there was a positive correlation between ferroptosis and hypoxia Z-score. 6 modules were obtained by Weighted Gene Co-Expression Network Analysis (WGCNA), and 2 key modules and 66 key genes were screened out. Genes in the key modules were found mainly related to ERK1 and ERK2 cascade, TNF signaling pathway, and MAPK signaling pathway through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Protein-protein interaction (PPI) network analysis was performed on the key genes and 10 hub genes (Atf3, Ptgs2, Cxcl1, Socs3, Hspa1b, Selp, Cxcl2, Il1b, Myd88, and S100a8) were obtained using STRING and Cytohubba. The expression of 9 hub genes except Cxcl1 was consistent in GSE4648 and GSE775. The transcription factors (TFs)-hub genes interaction network was constructed and 48 TFs were obtained using TRRUST. Finally, it was verified through the animal experiment that these hub genes were up-regulated in AMI mice myocardial tissues. This study offers new ideas for the diagnosis and treatment of AMI.