Abstract
BACKGROUND: Diabetic foot ulcers (DFUs) are one of the most common and serious complications of diabetes. OBJECTIVES: The objective of the study is to identify key genes and cellular mechanisms driving DFU pathogenesis and healing using multi-omics integration. METHODS: We used differential expression analysis and weighted co-expression network analysis (WGCNA) to identify key genes in DFU. We constructed protein-protein interaction (PPI) networks through STRING and Cytoscape. Support vector machine-recursive feature elimination (SVM-RFE) was used to screen out potential diagnostic biomarkers. Single-cell transcriptomic analysis detected differences in the cellular landscape, and intercellular communication analysis deciphered the key intercellular signaling pathway. RESULTS: We first found 388 differentially expressed genes that are closely related to DFU (fold change > 2 and WGCNA-derived module significantly correlated with DFU, R = 0.78). We further constructed a PPI network and identified 15 hub genes and 10 diagnostic biomarkers (including FGF7) for DFU. FGF7 is lowly expressed in DFU and enriched in stromal cells and fibroblasts in DFU, and participates in the immune microenvironment of DFU. FGF7-FGFR1 is the main pathway for intercellular communication involving fibroblasts and stromal cells in the healing process of DFU. CONCLUSIONS: These results provide an in-depth understanding of the multifactorial mechanisms underlying DFU progression and healing, offering a theoretical basis for optimizing clinical treatment.