Exploration of the Shared Gene Signatures and Molecular Mechanisms Between Diabetic Foot Ulcer and Diabetic Microvascular Disease

Background: Diabetic foot ulcer (DFU) is a serious complication of diabetes caused by multiple factors. Diabetic microvascular disease has a close linkage with DFU. However, the inter-relational mechanisms between them are still unclear. This article aimed to explore the shared gene signatures and potential molecular mechanisms in DFU and diabetic microvascular disease. Methods: In the GEO database, DFU microarray datasets (GSE80178, GSE68183) and diabetic microvascular disease microarray datasets (GSE43950) were downloaded. After data standardization processing, we used R software to analyze the transcriptome sequencing data of each data set to find the differentially expressed genes (DEGs) of DFU and diabetic microvascular disease. Then obtained the overlapped DEGs in DFU and diabetic microvascular disease database by Jvenn. Finally, the shared DEGs were enriched by pathway enrichment and protein-protein interaction (PPI) analysis, and the hub gene was found by node analysis. Results: Totally, 1007 DEGs were identified in the GSE80178 dataset, 338 DEGs were identified in the GSE68183 dataset, 1154 were identified in the GSE43950 dataset, Venn diagram analyses showed that there were 14 shared DEGs in these datasets. Enrichment analysis shows that the shared DEGs were mainly associated with chronic inflammatory response, leukocyte migration, cellular transition metal ion homeostasis, vascular wound healing, collagen-containing extracellular matrix and Toll-like receptor binding. Involved pathways were mainly enriched in IL-17 signaling, glycosaminoglycan degradation, and calcium signaling. PPI analysis of these shared DEGs shows that S100A9, S100A8, CSTA, ADAP2, CD34 and FGL2 were the hub gene whose plays a pivotal role in DFU.Conclusion: Our work has identified several new DFU candidate genes that can be used as biomarkers or potential therapeutic targets