Identification of VEGFB associated with NKT cells in diabetic foot ulcers: Single-cell analysis and machine learning

The management options for diabetic foot are restricted, and the outlook is unfavorable. Immune cells have been implicated in diabetic foot ulcer (DFU), but the exact role of natural killer T (NKT) cells in DFU remains unclear. Vascular endothelial growth factor B (VEGFB), a member of the VEGF family, is distinguished by its potential roles in metabolic regulation and immune modulation, yet its connection to NKT cells in DFU is unexplored. This study was to identify specific genes associated with NKT cells in DFU and to ascertain potential targets. We analyzed single-cell ribonucleic acid sequencing and bulk transcriptome data from DFU datasets. Differential expression analysis identified genes associated with NKT cells in DFU. Machine learning algorithms were applied to pinpoint the most significant genes from these candidates. The functional characteristics of the identified key gene were further investigated through gene set enrichment analysis and immune infiltration analysis. Single-cell analysis revealed 390 NKT cell-related genes, and differential analysis identified 728 differentially expressed genes. Cross-referencing yielded 37 NKT cell-related differentially expressed genes. Machine learning consistently identified VEGFB as a key biomarker. Functional analysis linked VEGFB to cell adhesion, vasculature development, and angiogenesis pathways. VEGFB was significantly overexpressed in DFU samples compared to controls. Our study identifies VEGFB as a valuable biomarker associated with NKT cells in DFU. The overexpression of VEGFB suggests its involvement in DFU pathogenesis, potentially bridging immune regulation and vascular pathways. This finding enhances the understanding of NKT cell mechanisms in DFU and positions VEGFB as a potential target for future diagnostic and therapeutic strategies aimed at immunomodulation.