Circular RNAs hsa-circ0000175 and hsa-circ0044235 in plasma are novel biomarkers for new-onset rheumatoid arthritis

Circular RNAs (circRNAs) are a class of non-coding RNAs that could serve as potential molecular markers for disease diagnosis. However, the role of circRNAs in plasma from new-onset rheumatoid arthritis (RA) has not been extensively investigated. In this study, the expression of hsa-circ0000175 and hsa-circ0044235 in plasma from RA patients, healthy controls (HCs), systemic lupus erythematosus (SLE) patients, osteoarthritis (OA), and undiagnosed arthritis (UA) patients were determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Correlation analysis was used to assess the correlation of the two circRNAs and clinical variables of RA. The receiver operating characteristic (ROC) curves were created to evaluate the diagnostic value and multivariate analysis (logistic regression) was performed to analyse the risk factors. We confirmed that hsa-circ0000175 was significantly elevated in plasma from patients with new-onset RA compared with HC and patients with new-onset SLE, but significantly was reduced when compared with OA + UA patients. Hsa-circ0044235 was found to be significantly decreased in plasma from patients with new-onset RA compared with HC and OA + UA patients, but was significantly increased compared with SLE patients. The expression of plasma hsa-circ0000175 in new-onset RA patients was associated with platelet count (PLT), plateletcrit (PCT), and platelet large cell ratio (PLR), the expression of plasma hsa-circ0044235 new-onset RA patients was associated with swollen joint count (SJC), painful joint count (PJC), and disease activity score 28 (DAS28). ROC curve analysis suggested that the combination of hsa-circ0000175 and hsa-circ0044235 has some value in the diagnosis of new-onset RA from HC, patients with SLE and patients with OA + UA. The logistic regression analysis revealed that the expression of hsa-circ0000175 and hsa-circ0044235 in plasma were risk factors for RA. This study suggests that the combination of plasma hsa-circ0000175 and hsa-circ0044235 improves the diagnostic accuracy for new-onset RA. Moreover, the expression levels of plasma hsa-circ0000175 and hsa-circ0044235 were associated with disease activity and severity of RA.

环状RNA（Circular RNAs, circRNAs）是一类非编码RNA，可作为疾病诊断的潜在分子标志物。然而，环状RNA在新发类风湿关节炎（rheumatoid arthritis, RA）患者血浆中的作用尚未得到广泛研究。本研究通过定量逆转录聚合酶链反应（quantitative reverse transcription-polymerase chain reaction, qRT-PCR）检测了RA患者、健康对照（healthy controls, HCs）、系统性红斑狼疮（systemic lupus erythematosus, SLE）患者、骨关节炎（osteoarthritis, OA）及未确诊关节炎（undiagnosed arthritis, UA）患者血浆中hsa-circ0000175和hsa-circ0044235的表达水平。采用相关性分析评估两种环状RNA与RA临床变量的相关性；绘制受试者工作特征（receiver operating characteristic, ROC）曲线以评价其诊断价值，并通过多因素分析（logistic回归, logistic regression）分析风险因素。本研究证实，与健康对照及新发SLE患者相比，新发RA患者血浆中hsa-circ0000175的表达显著升高，但与OA+UA患者相比则显著降低。研究发现，与健康对照及OA+UA患者相比，新发RA患者血浆中hsa-circ0044235的表达显著降低，但与SLE患者相比则显著升高。新发RA患者血浆hsa-circ0000175的表达水平与血小板计数（platelet count, PLT）、血小板压积（plateletcrit, PCT）及大血小板比率（platelet large cell ratio, PLR）相关；新发RA患者血浆hsa-circ0044235的表达水平与肿胀关节计数（swollen joint count, SJC）、压痛关节计数（painful joint count, PJC）及疾病活动度评分28（disease activity score 28, DAS28）相关。ROC曲线分析显示，hsa-circ0000175与hsa-circ0044235的联合检测在区分新发RA与健康对照、SLE患者及OA+UA患者的诊断中具有一定价值。Logistic回归分析表明，血浆hsa-circ0000175和hsa-circ0044235的表达水平是RA的风险因素。本研究提示，血浆hsa-circ0000175与hsa-circ0044235的联合检测可提升新发RA的诊断准确性。此外，血浆hsa-circ0000175与hsa-circ0044235的表达水平与RA的疾病活动度及严重程度相关。