Identification of novel ferroptosis-related biomarkers associated with the oxidative stress pathways in ischemic cardiomyopathy

Background: Ferroptosis is a cell death process that depends on iron and reactive oxygen species. It significantly contributes to cardiovascular diseases. However, its exact role in ischemic cardiomyopathy (ICM) is still unclear.

Methods: Using bioinformatics methods, we identified new molecular targets associated with ferroptosis in ICM and conducted various analyses-including correlation analysis, pathway enrichment analysis, protein interaction network construction, and analysis of transcription factor and drug interactions, to reveal the potential mechanisms behind these genes.

Results: We evaluated two independent training sets of ICM, GSE57338 and GSE5406, comprising 203 ICM samples, and validation sets GSE76701 to examine differentially expressed genes (DEGs) related to ferroptosis. After extracting the intersection of the gene sets and ferroptosis-related genes, 53 DEGs were identified. Enrichment analyses showed that the alterations in ferroptosis-related DEGs were mainly enriched in oxidative stress response, and immune-related pathways. Furthermore, 11 hub genes were identified using protein-protein interaction network analysis. The key interactions between 11 hub genes were more pronounced in protein localization during ICM development. In addition, we construct a hub gene and transcription factor interaction network and a small molecule drug-gene interaction network. We found that among these hub genes, the N-acetylneuraminate outer membrane channel(NANC) gene is positively correlated with most of the small-molecule drugs used to treat ICM, and its high expression might increase resistance.

Conclusions: Ferroptosis exists in ICM and and is associated with oxidative stress. This association suggests that ferroptosis may facilitate the progression of ICM.