Identification of Heme Metabolism-Related Biomarkers in Keloids Using Transcriptomic Analysis and Cultured Human...

Keloid is a fibroproliferative disorder with high recurrence and unclear pathogenesis, lacking effective therapeutic targets. Recent evidence suggests metabolic reprogramming, particularly in heme metabolism, may drive fibrosis. This study investigates the role of heme metabolism, focusing on feline leukemia virus subgroup C receptor 1 (FLVCR1), in keloid pathogenesis and explores its diagnostic and therapeutic potential. We analyzed bulk RNA-seq datasets and single-cell RNA-seq data (scRNA-seq). Differential expression, least absolute shrinkage and selection operator (LASSO), and random forest (RF) models identified heme metabolism-related diagnostic biomarkers. Immune infiltration, single-cell mapping, microRNA (miRNA) network construction, and molecular docking with traditional Chinese medicine compounds were performed. Six heme metabolism-related biomarkers were identified, forming a diagnostic nomogram with high accuracy. FLVCR1, enriched in endothelial cells and melanocytes, correlated negatively with T follicular helper cells, suggesting immunometabolic crosstalk. MiRNA regulatory network analysis revealed five miRNAs co-targeting all six biomarkers. Molecular docking identified (+)-gallocatechin as a high-affinity FLVCR1 ligand. These findings suggest an association between FLVCR1-related heme metabolism and immune alterations in keloid pathogenesis. The biomarker panel showed exploratory diagnostic potential, and (+)-gallocatechin was identified as a candidate FLVCR1-interacting compound requiring further validation. This study reframes keloid within the metabo-fibrotic spectrum and proposes metabolic-immune intervention as a novel therapeutic strategy.