Identification and verification of ferroptosis‐related genes in diabetic foot using bioinformatics analysis

Abstract

Ferroptosis is a novel form of cell death that plays a key role in several diseases, including inflammation and tumours; however, the role of ferroptosis‐related genes in diabetic foot remains unclear. Herein, diabetic foot‐related genes were downloaded from the Gene Expression Omnibus and the ferroptosis database (FerrDb). The least absolute shrinkage and selection operator regression algorithm was used to construct a related risk model, and differentially expressed genes were analysed through immune infiltration. Finally, we identified relevant core genes through a protein–protein interaction network, subsequently verified using immunohistochemistry. Comprehensive analysis showed 198 genes that were differentially expressed during ferroptosis. Based on functional enrichment analysis, these genes were primarily involved in cell response, chemical stimulation, and autophagy. Using the CIBERSORT algorithm, we calculated the immune infiltration of 22 different types of immune cells in diabetic foot and normal tissues. The protein–protein interaction network identified the hub gene TP53, and according to immunohistochemistry, the expression of TP53 was high in diabetic foot tissues but low in normal tissues. Accordingly, we identified the ferroptosis‐related gene TP53 in the diabetic foot, which may play a key role in the pathogenesis of diabetic foot and could be used as a potential biomarker.

The role of programmed cell death in diabetic foot ulcers

“…Finally, they screened out the iron deathrelated gene TP53, which may play a key role in the pathogenesis of diabetic foot ulcers and can serve as a potential biomarker. 76 In addition, studies have shown that MAFG and MAPK3 act as death-related genes that are relevant to DFUs and may become potential therapeutic targets for DFU patients. The higher accuracy of MAPK3 suggests that it may be a promising iron death-related biomarker.…”