COL14A1 drives ischemic cardiac injury in PCOS: an artificial intelligence-identified biomarker

BACKGROUND: Polycystic ovary syndrome (PCOS) and ischemic cardiomyopathy (ICM) share metabolic and cardiovascular risk factors, including insulin resistance and chronic inflammation, but the molecular links remain unclear. AIM: To identify shared diagnostic biomarkers between PCOS and ICM and clarify their biological basis. METHODS: Transcriptomic datasets from multiple PCOS and ICM GEO cohorts were integrated. Differential expression analysis, WGCNA, and 105 machine-learning model combinations were applied to identify robust cross-disease biomarkers. The top-performing Elastic Net (Enet) model was used to screen candidate genes. Immune infiltration, single-cell RNA sequencing (scRNA-seq), and spatial transcriptomics defined cell-type specificity and tissue localization. Drug-target interactions were explored by molecular docking. RESULTS: Eleven candidate genes were identified, and COL14A1 was the only gene consistently validated across all independent datasets. scRNA-seq identified COL14A1 enrichment in TPM2+ activated fibroblasts, and cell-cell communication analysis highlighted a macrophage-fibroblast crosstalk axis. Spatial transcriptomics confirmed that COL14A1 is tightly linked to fibroblast activation, supporting its role as a mediator of immune-fibrotic responses during postischemic cardiac remodelling. Molecular docking revealed that rofecoxib is a high-affinity potential therapeutic agent targeting COL14A1. CONCLUSIONS: COL14A1 may represent a shared molecular link between PCOS and increased susceptibility to ischemic cardiac injury, potentially acting through macrophage-associated immune activation and fibroblast-mediated ECM remodelling. Rofecoxib may serve as a potential repurposed therapeutic candidate pending further validation. These findings provide mechanistic insights into the ovario-cardiac axis and highlight COL14A1 as a promising target for future risk stratification and intervention studies in women with PCOS.