AB0042\u2005THREE HEMATOLOGIC/IMMUNE SYSTEM-SPECIFIC EXPRESSED GENES ARE CONSIDERED AS THE POTENTIAL BIOMARKERS FOR THE DIAGNOSIS OF EARLY RHEUMATOID ARTHRITIS THROUGH BIOINFORMATICS ANALYSIS

Abstract

Rheumatoid arthritis (RA) is a common chronic autoimmune connective tissue disease that mainly involves the joints. The incidence of RA is 5 to 10 per 1000 people[1]. Early diagnosis and treatment of RA can effectively prevent disease progression, joint damage, and other complications in 90% of patients[2]. At present, serum biomarkers used in the diagnosis of established RA are rheumatoid factor and anti-cyclic citrullinated peptide antibody[3]. However, early RA especially serum RF and anti-CCP antibody-negative is difficult to diagnose due to the lack of effective biomarkers. Therefore, it is vital to identify new and effective biomarkers for the early diagnosis and treatment of RA.This study aimed to identify new biomarkers and mechanisms for RA disease progression at the transcriptome level through a combination of microarray and bioinformatics analyses.Microarray datasets for synovial tissue in RA or osteoarthritis (OA) were downloaded from the Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) were identified by R software. Tissue/organ-specific genes were recognized by BioGPS. Enrichment analyses were performed and protein-protein interaction (PPI) networks were constructed to understand the functions and enriched pathways of DEGs and to identify hub genes. Cytoscape was used to construct the co-expressed network and competitive endogenous RNA (ceRNA) networks. Biomarkers with high diagnostic value for the early diagnosis of RA were validated by GEO datasets. The ggpubr package was used to perform statistical analyses with Student’s t-test.A total of 275 DEGs were identified between 16 RA samples and 10 OA samples from the datasets GSE77298 and GSE82107. Among these DEGs, 71 tissue/organ-specific expressed genes were recognized. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that DEGs are mostly enriched in immune response, immune-related biological process, immune system, and cytokine signal pathways. Fifteen hub genes and gene cluster modules were identified by Cytoscape. Eight haematologic/immune system-specific expressed hub genes were verified by GEO datasets. GZMA, PRC1, and TTK may be biomarkers for diagnosis of early RA through combined the analysis of the verification results and the receiver operating characteristic (ROC) curve. NEAT1-miR-212-3p/miR-132-3p/miR-129-5p-TTK, XIST-miR-25-3p/miR-129-5p-GZMA, and TTK_hsa_circ_0077158- miR-212-3p/miR-132-3p/miR-129-5p-TTK might be potential RNA regulatory pathways to regulate the disease progression of early RA.This work identified three haematologic/immune system-specific expressed genes, namely, GZMA, PRC1, and TTK, as potential biomarkers for the early diagnosis and treatment of RA and provided insight into the mechanisms of disease development in RA at the transcriptome level. In addition, we proposed that NEAT1-miR-212-3p/miR-132-3p/miR-129-5p-TTK, XIST-miR-25-3p/miR-129-5p-GZMA, and TTK_hsa_circ_0077158-miR-212-3p/miR-132-3p/miR-129-5p-TTK are potential RNA regulatory pathways that control disease progression in early RA.[1]Smolen JS, Aletaha D, McInnes IB: Rheumatoid arthritis.Lancet 2016, 388:2023-2038.[2]Aletaha D, Smolen JS: Diagnosis and Management of Rheumatoid Arthritis: A Review.Jama 2018, 320:1360-1372.[3]Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO, 3rd, Birnbaum NS, Burmester GR, Bykerk VP, Cohen MD, et al: 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative.Arthritis Rheum 2010, 62:2569-2581.None declared