NCOA1 and PRPS1 as novel metabolism-related biomarkers in myocardial ischemia–reperfusion injury

Mitochondrial metabolism (MM) plays a critical role in myocardial ischemia–reperfusion injury (MIRI), yet reliable metabolism-related biomarkers for this condition remain largely unexplored. Here, we integrated transcriptomic datasets from public repositories with MM-related gene sets to identify candidate biomarkers in MIRI. Through weighted gene co-expression network analysis (WGCNA), differential expression profiling, and two machine learning algorithms (SVM-RFE and Boruta), we screened candidate genes and validated their expression in both independent GEO cohorts and clinical whole-blood samples via RT-qPCR. Two candidate biomarkers, NCOA1 and PRPS1 , were consistently identified and validated, showing opposing expression patterns in MIRI versus controls. Immune infiltration analysis revealed significant correlations between the estimated abundance of M0 macrophages and both candidate biomarkers, indicating an association between these molecular and immune-related features. Pathway enrichment analyses further identified associations with ribosomal function and nucleotide metabolism, providing potential directions for further mechanistic investigation. Notably, molecular docking yielded moderate docking scores for the predicted biomarker–drug pairs, including NCOA1–methylthioninium and PRPS1–thioguanine, warranting further experimental evaluation. Collectively, our findings identify NCOA1 and PRPS1 as candidate metabolism-related biomarkers selected through an MRG-based screening framework, which warrant further validation in larger independent cohorts and mechanistic studies.