Abstract
BACKGROUND: Diabetic foot ulcers (DFU) are severe complications with complex pathogenesis involving inflammation and impaired healing. Taurine, a key antioxidant amino acid, shows therapeutic potential in diabetes, but its role in DFU remains unclear and warrants investigation. METHODS: This integrated multi-omics study analyzed DFU using GEO transcriptomics data (training: GSE68183/GSE80178; validation: GSE37265/GSE134431; scRNA-seq: GSE223964). Limma identified DEGs that intersected with taurine metabolism -related genes. Key modules (MCODE) and a LASSO-based diagnostic signature were established. Immune infiltration was profiled via ssGSEA, CIBERSORT, and MCP-Counter. Regulatory networks (TFs/miRNAs) were predicted (miRNet/NetworkAnalyst), and therapeutic agents were screened (DSigDB). Seurat-processed scRNA-seq defined nine cell types, with CellChat analyzing intercellular communication. RESULTS: This study identified a three-gene diagnostic signature (HMOX1, MAPK3, TXN) for DFU with near-perfect accuracy (training AUC = 1, validation AUC ≥ 0.98). Multi-omics analyses revealed significant immune dysregulation (increased B cells/CD8(+)T cells/M1 macrophages in DFS), collagen-centric signaling dominance, and two molecular subtypes. Single-cell RNA-seq uncovered cell-type-specific dysfunction: fibroblasts and endothelial cells expanded in DFS, while HMOX1 localized to Mono-macrophages and MAPK3 to endothelium. CONCLUSION: This study deeply analyzed DFU immune microenvironment characteristics, intercellular communication networks, and molecular regulatory mechanisms, revealing a dysregulated metabolic-immune repair network framework, providing new insights for understanding DFU pathological mechanisms and developing targeted diagnostic and therapeutic strategies.