Identification of Potential Biomarkers in Synovial Tissue of Rheumatoid Arthritis via Integrated Microarray Analysis. Identification of Biomarkers of Rheumatoid Arthritis

Abstract Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovitis and subsequent destruction of cartilage and bone. This study aimed to explore RA-related gene markers and the underlying molecular mechanism.Material and Methods: The expression profiles of GSE77298, GSE55235 and GSE12021 were obtained from the Gene Expression Omnibus database. Then, the differential gene expression analysis was conducted between GSE77298 and GSE55235 datasets. Limma package and a Venn diagram were utilized to screen the overlapping differentially expressed genes (DEGs), and Functional enrichment and pathway analysis were performed by using DAVID database. Subsequently, a protein-protein interaction (PPI) network was established, and candidate hub genes were recognized by using STRING and Cytoscape software. Finally, another dataset (GSE12021) was used for the validation of diagnostic value of the candidate hub genes and to identify real hub genes by using receiver operating characteristic (ROC) curves.Results: A total of 385 DEGs were detected, which include 19 downregulated genes and 366 upregulated genes. GO and KEGG pathway analysis showed that DEGs was mainly enriched in various immune and inflammatory response-related functions and pathways. The PPI network was composed of 374 nodes and 767 edges. A total of 8 real hub genes (HLA-DRA, HLA-DRB1, LCK, VAV1, HLA-DPA1, HLA-DPB1, C3AR1 and CD3D) which displayed an excellent diagnostic value for RA were identified.Conclusion: these findings may provide novel and reliable biomarkers for RA, which have some interesting implications for early diagnosis, prognosis and targeted therapy.