CircRNA_0001412 and CircRNA_0001566 as Potential Biomarkers for the Diagnosis of Rheumatoid Arthritis.

Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disease with high disability rates, necessitating early diagnosis. This study investigated the potential of circRNAs, specifically CircRNA_0001412 and CircRNA_0001566, as diagnostic biomarkers for RA. High-throughput transcriptome sequencing was performed on peripheral blood mononuclear cells (PBMCs) from RA patients and healthy controls to identify differentially expressed circRNAs. Reverse transcription quantitative PCR (RT-qPCR) was used to validate circRNA expression in an independent cohort of 78 RA patients and 82 healthy controls. Receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic value of the selected circRNAs. Correlation analyses with clinical markers such as CRP, ESR, CCP, RF, WBC, lymphocyte count, and monocyte count were also conducted. Bioinformatics analyses, including GO and KEGG pathway enrichment, were conducted to explore the functional roles of the identified circRNAs and associated miRNAs. A total of 54 circRNAs were identified as differentially expressed in RA, with 21 circRNAs upregulated and 33 downregulated. Among these, CircRNA_0001412 and CircRNA_0001566 were highly expressed in RA PBMCs and demonstrated good sensitivity and specificity as diagnostic biomarkers (AUC = 0.751 (95%CI 0.673, 0.830) and 0.605(95%CI 0.516, 0.694)). Combined analysis of these circRNAs further improved diagnostic performance (AUC = 0.776 (95%CI 0.702, 0.851)). Notably, CircRNA_0001412 showed a significant correlation with CRP, suggesting its potential as a biomarker for RA disease severity. Bioinformatics analysis predicted that CircRNA_0001412 and CircRNA_0001566 could promote T-cell activation via the PI3K-Akt signaling pathway, contributing to RA pathogenesis. CircRNA_0001412 and CircRNA_0001566 are promising diagnostic biomarkers for RA, with CircRNA_0001412 additionally serving as a potential indicator of inflammatory activity. These findings provide a basis for further research into the diagnostic and prognostic utility of circRNAs in RA.