Identification of hub genes in rheumatoid arthritis tissue-derived extracellular vesicles

Abstract

Abstract Background: Rheumatoid arthritis (RA) is a chronic autoimmune connective tissue disease. However, effective diagnostic biomarkers for RA are lacking. This study aimed to validate tissue-derived extracellular vesicles (Ti-EVs) as biomarkers for RA. Ti-EVs were isolated from the joints of a collagen-induced arthritis rat model, analysed, and subjected to potential biomarker identification. Differentially expressed genes (DEGs) were identified and analysed for functional enrichment. Datasets were obtained from the Gene Expression Omnibus, and DEGs were obtained using NCBI GEO2R. GSE55235 was used to compare the shared Ti-EV DEGs. Protein–protein interaction network analysis was performed to identify the hub genes. GES89408 was used to analyse gene expression, and the diagnostic value of the genes was assessed using receiver operating characteristic (ROC) curves. Results: In total, 1,725 DEGs and 186 co-expressed genes were identified in the sequencing and GSE55235 datasets, respectively. Functional enrichment analysis showed that the enriched pathways for the DEGs were related to RA. ROC analysis showed that the hub genes CXCR4, CD8A, CCR5, CD40LG, CCL5, CD2, PRF1, FCGR3B, and IL2RGcould effectively be used for the diagnosis of RA, of which FCGR3B and IL2RG were the most specific and sensitive, respectively, for early-stage RA. Conclusions: Ti-EV-related information can help elucidate RA pathogenesis. The novel DEGs and functional pathways identified in this study will facilitate future research on RA.