Circular RNAs Hsa_circ_0002715 and Hsa_circ_0035197 in Peripheral Blood Are Novel Potential Biomarkers for New-Onset Rheumatoid Arthritis.

Abstract

This study is aimed at exploring the levels of peripheral blood circular RNAs (circRNAs) as biomarker candidates for the diagnosis of new-onset rheumatoid arthritis (RA). The selected twenty-two circRNAs in peripheral blood from new-onset RA patients and healthy controls (HC) were determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The levels of hsa_circ_0002715, hsa_circ_0001947, hsa_circ_0000367, and hsa_circ_0035197 were significantly increased in the peripheral blood of new-onset RA patients than in the peripheral blood of HC. And, there were obvious differences in the above four peripheral blood circRNAs between new-onset RA patients and systemic lupus erythematosus (SLE) patients and ankylosing spondylitis (AS) patients. Moreover, there were obvious differences in hsa_circ_0001947 and hsa_circ_0035197 between new-onset RA patients and patients with undiagnosed arthritis (UA). Receiver operating characteristic (ROC) curve analysis suggested that the levels of hsa_circ_0002715 and hsa_circ_0000367 in peripheral blood could distinguish new-onset RA patients from the HC, AS patients, and SLE patients, and the levels of hsa_circ_0001947 and hsa_circ_0035197 in peripheral blood could distinguish new-onset RA patients from the HC, AS patients, SLE patients, and UA patients. The logistic regression model showed that the combination of hsa_circ_0002715 and hsa_circ_0035197 could provide the best diagnostic accuracy with an area under the curve (AUC) of 0.758 (sensitivity: 72.9%, specificity: 71.4%). Moreover, the levels of peripheral blood hsa_circ_0002715 were correlated with swollen joint count (SJC), tender joint count (TJC), disease duration, rheumatoid factor (RF), anticitrullinated protein antibodies (ACPA), and hematologic disorder. And, the levels of peripheral blood hsa_circ_0035197 were correlated with hematologic disorder. This study suggests that the combination of hsa_circ_0002715 and hsa_circ_0035197 in peripheral blood may be a potential biomarker of patients with new-onset RA and may be associated with disease activity.