Exploring the pathogenesis of osteomyelitis accompanied by diabetic foot ulcers using microarray data analysis.

Abstract

Although numerous studies have shown distinctive similarities between osteomyelitis and diabetic foot ulcers (DFU), the common pathogenesis of both is not fully understood. The current research focuses on an in-depth study of the molecular and pathway mechanisms involved in the complication of these 2 diseases. We downloaded clinical information on osteomyelitis (GSE30119) and DFU (GSE29221) from the GEO database, along with gene expression matrices. Differentially expressed genes (DEGs) among normal individuals and patients with osteomyelitis; normal individuals and patients with DFU were identified by R software, and thus common DEGs were confirmed. We then analyzed these differential genes, including the functional pathway analysis, protein-protein interaction (PPI), modules and hub genes establishment, and transcription factor regulatory networks. We identified 109 common DEGs (46 up-regulated and 63 down-regulated genes) for subsequent analysis. The results of PPI network and the functional pathway analysis revealed the importance of immune response and inflammatory response in both diseases. Among them, chemokines and cytokines were found to be closely related to both osteomyelitis and DFU. In addition, the tumor necrosis factor (TNF) pathway and Staphylococcus aureus infection were found to have more significant roles too. The 12 most essential key genes were later screened by cytoHubba, including matrix metalloproteinases (MMP) 1, MMP3, MMP9, IL8, C-X-C chemokine receptor (CXCR) 2, C-X-C motif chemokine ligand (CXCL) 9, CXCL10, CXCL13, FCGR3B, IL1B, LCN2, S100A12. CXCL10, and MMP1 were validated using the least absolute shrinkage and selection operator (LASSO) and support vector machine-recursive feature elimination (SVM-RFE) algorithms. Osteomyelitis and DFU share similar molecular and pathway mechanisms. These common key genes and pathways may provide new directions toward the future study of osteomyelitis and DFU.