Potential novel diagnostic biomarkers of atrial fibrillation: four ferroptosis-related genes linking immune infiltration.

BACKGROUND: Atrial fibrillation (AF) is a common atrial arrhythmia in clinic, regulated by the immune system and associated with ferroptosis. We hypothesized that combining the analysis of ferroptosis and immune infiltration in AF will help identify more precise diagnostic biomarkers. METHODS: We analyzed two gene expression omnibus (GEO) data sets (GSE41177 and GSE122188) and extracted characteristic ferroptosis-related genes related to sinus rhythm and AF via bioinformatic analysis. CIBERSORT was used to identify ferroptosis/immune-related genes (FIRGs) in AF. LASSO model analysis was used to identify novel FIRGs. The GSE79768 data set and qRT-PCR were used to validate the FIRGs. ROC curves were then drawn to evaluate the diagnostic power of the FIRGs, and GSEA was used to detect the pathways enriched with the validated FIRGs. RESULTS: A total of eight FIRGs were identified between the healthy and AF groups through LASSO model analysis. Four FIRGs (ALOX15, SNX5, CA9, and PROK2) were subsequently validated as novel FIRGs with high diagnostic power for AF (AUC = 0.851-0.911). They were enriched mainly in cytokine-cytokine receptor interactions, ascorbate and aldarate metabolism, the nod-like receptor signaling pathway, and the intestinal immune network for IgA production. In addition, ceRNA networks (mRNA-miRNA-lncRNA) such as SNX5-hsa-miR-185-3p-LINC01165 and PROK2-hsa-miR-125b-2-3p-RP11-333E1.2 were constructed. Candidate drugs, such as linoleic acid, which is targeted by ALOX15, and sulfamide, targeted by CA9, were also identified. CONCLUSIONS: Our findings reveal the significant ferroptosis/immune-related genes and the potential pathways and biofunctions enriched with these genes in AF and provide new insights for the diagnosis and interference of AF.