Plasma Proteomics-Based Identification of Novel Predictive and Diagnostic Inflammatory Biomarkers for Diabetic Foot

Diabetic foot ulceration (DFU) is a severe complication of diabetes characterized by chronic inflammation, yet its underlying mechanisms remain unclear. This study aimed to identify plasma inflammatory biomarkers distinguishing diabetic foot (DF) patients from those with diabetes (DM) and healthy controls (NC). Using proximity extension assay (PEA) technology, we analyzed 92 inflammation-related proteins in fasting plasma samples from NC (<i>n</i> = 10), DM (<i>n</i> = 10), and DF (<i>n</i> = 10) groups. Compared to DM patients, DF patients exhibited significant upregulation of 21 cytokines. Among these, MCP-4, SLAMF1, CD5, CSF-1, and FGF-5 demonstrated high diagnostic potential with AUC values ranging from 0.84 to 0.92. ELISA validation confirmed the elevated expression of MCP-4, SLAMF1, and CSF-1 in DF patients. Functional enrichment analysis linked these proteins to inflammatory pathways (e.g., cytokine-cytokine receptor interaction) and macrophage activation. This study highlights MCP-4, SLAMF1, and CSF-1 as novel predictive biomarkers for DF, providing insights into its pathogenesis and diagnostic strategies.