Ouyang Qingqing, Wu Jing, Jiang Zhenlan, Zhao Jinjun, Wang Ran, Lou Aiju, Zhu Dingji, Shi Guo-Ping, Yang Min
Department of Rheumatology and Immunology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Cell Physiol Biochem. 2017;42(2):651-659. doi: 10.1159/000477883. Epub 2017 Jun 15.
BACKGROUND/AIMS: Circular RNAs (circRNAs) compose a large class of RNAs that can be used as biomarkers in clinical blood samples. This study aimed to determine the expression of circRNAs in peripheral blood mononuclear cells (PBMCs) from rheumatoid arthritis (RA) patients to identify novel biomarkers for RA screening.
We started with a microarray screening of circRNA changes in PBMCs from 5 RA patients and 5 healthy controls. We then confirmed the selected circRNA changes in PBMCs from 30 RA patients and 25 age- and sex-matched controls using the real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Spearman correlation test was performed to assess the correlation of circRNAs and clinical variables. Receiver operating characteristic (ROC) curve was calculated to evaluate the diagnostic value.
We identified and verified five circRNAs (092516, 003524, 103047, 104871, 101873) that were significantly elevated in PBMCs from RA patients. Among these RA patients, we detected no significant correlation between the five circRNAs and the disease severity, including disease activity score (DAS28), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and health assessment questionnaire (HAQ). Yet, ROC curve analysis suggested that circRNA_104871 has significant value of RA diagnosis (AUC=0.833, P<0.001), followed by circRNA_003524 (AUC = 0.683, P = 0.020), circRNA_101873 (AUC = 0.676, P = 0.026), and circRNA_103047 (AUC = 0.671, P = 0.030).
This study suggests that increased expression of circRNAs circRNA_104871, circRNA_003524, circRNA_101873 and circRNA_103047 in PBMC from RA patients may serve as potential biomarkers for RA patient diagnosis.
背景/目的：环状RNA（circRNAs）构成了一大类RNA，可作为临床血液样本中的生物标志物。本研究旨在确定类风湿关节炎（RA）患者外周血单个核细胞（PBMC）中circRNAs的表达情况，以识别用于RA筛查的新型生物标志物。
我们首先对5例RA患者和5例健康对照的PBMC进行circRNA变化的微阵列筛选。然后，我们使用实时定量逆转录-聚合酶链反应（qRT-PCR），在30例RA患者和25例年龄及性别匹配的对照的PBMC中，对选定的circRNA变化进行了验证。进行Spearman相关性检验，以评估circRNAs与临床变量之间的相关性。计算受试者工作特征（ROC）曲线，以评估诊断价值。
我们鉴定并验证了5种在RA患者的PBMC中显著升高的circRNAs（092516、003524、103047、104871、101873）。在这些RA患者中，我们未检测到这5种circRNAs与疾病严重程度之间存在显著相关性，疾病严重程度包括疾病活动评分（DAS28）、红细胞沉降率（ESR）、C反应蛋白（CRP）和健康评估问卷（HAQ）。然而，ROC曲线分析表明，circRNA_104871具有显著的RA诊断价值（AUC = 0.833，P < 0.001），其次是circRNA_003524（AUC = 0.683，P = = 0.020）、circRNA_101873（AUC = 0.676，P = 0.026）和circRNA_103047（AUC = 0.671，P = 0.030）。
本研究表明，RA患者PBMC中circRNAs circRNA_104871、circRNA_003524、circRNA_101873和circRNA_103047表达增加，可能作为RA患者诊断的潜在生物标志物。
