Bioinformatics analysis of ferroptosis-related genes in the pathogenesis of diabetic ulcers

Abstract Background: Diabetic ulcers are a major complication of diabetes which causing lower extremity amputation. Nonetheless, the progression in the development of diabetic ulcers therapeutics is slow. Ferroptosis plays a key role in the pathogenesis of chronic wound in diabetic ulcers. The mechanism needs to be further clarified. Methods: Ferroptosis-related differentially expressed genes (FRDEGs) in diabetic ulcers were screened from the dataset GSE92724 and FerrDb online database based in silico. Then, functional enrichment analysis and protein-protein interaction (PPI) network were implemented to recognize the potential biological pathways and mechanisms. MCODE tool was used to cluster and predict hub genes. The miRNAs corresponding to hub genes were predicted by miRWalk 2.0. Receiver operating characteristic (ROC) was applied to verify the diagnostic value of five hub genes in the dataset GSE132187 and GSE134431. The immune infiltration between diabetic ulcers samples and normal samples were analyzed by using CIBERSORTx. Results: 26 FRDEGs and 5 hub genes (EGFR, SLC2A1, CD44, CA9, and PTGS2) in diabetic ulcers were identified. GO and KEGG analysis revealed that hub genes were significantly enriched in response to oxidative stress, basolateral plasma membrane, and HIF-1 signaling pathway. ROC results suggested that hub genes have a high diagnostic accuracy for diabetic ulcers. In immune cell infiltration, T follicular helper cells and monocytes were significantly lower in diabetic ulcers. Conclusion: This research firstly demonstrated that five hub genes may be potential therapeutic targets and possible diagnostic biomarkers in the pathogenesis of diabetic ulcers.