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microRNA-132 及其靶基因 NAG-1 对评估非甾体抗炎药治疗强直性脊柱炎患者疗效的预测价值。

Predictive value of microRNA-132 and its target gene NAG-1 in evaluating therapeutic efficacy of non-steroidal anti-inflammatory drugs treatment in patients with ankylosing spondylitis.

机构信息

The Second Department of Orthopaedics, Xianyang Central Hospital, Xianyang, 712000, People's Republic of China.

The Second Department of Orthopaedics, Shaanxi Traditional Chinese Medicine Hospital, Xi'an, 710003, People's Republic of China.

出版信息

Clin Rheumatol. 2018 May;37(5):1281-1293. doi: 10.1007/s10067-018-4017-2. Epub 2018 Mar 1.

Abstract

Ankylosing spondylitis (AS) is a common chronic rheumatic disorder, accompanied by the differential expression of various microRNAs (miRNAs) in patients suffering from the condition, some of which have the potential to serve as novel complementary AS biomarkers. During this study, AS patients were recruited in connection with our investigation into the correlation of microRNA-132 (miR-132) in peripheral blood and its target gene NAG-1 expressions in relation with the clinical efficacy of non-steroidal anti-inflammatory drugs (NSAIDs) treatment in patients with AS. A total of 218 AS patients who had been previously treated with oral diclofenac sodium and were placed into either the response (n = 175) or non-response groups (n = 43) following a 16-week period of therapeutic evaluation. An additional 113 healthy patients were also recruited for the purposes of the study. AS patient peripheral blood samples were obtained at the 0th, 8th, and 16th week, with the corresponding samples of the healthy patients collected at week 0. The expressions of miR-132 and NAG-1 were detected by RT-qPCR and analyzed using a ROC curve for the elucidation of the diagnostic value of peripheral blood miR-132 expressions as well as their predictive value among AS patients undergoing NSAIDs treatment. The targeting relations of miR-132 and NAG-1 were validated by microRNA.org and luciferase assay. Greater levels of peripheral blood miR-132 expression were observed among AS patients prior to treatment, in comparison to the healthy patients in the study. Prior to treatment, the area under the miR-132 ROC curve (AUC) of AS patients was 0.965, with a critical point of 2.605. The sensitivity and specificity of miR-132 were 91.7 and 97.3%, respectively, in regard to the AS diagnostic clinical efficacy. In comparison with the non-response group, the miR-132 expression of patients in the response group exhibited descended levels while the mRNA expression of NAG-1 increased. The ROC results indicated that the AUC of miR-132 was 0.876 with its sensitivity and specificity observed to be 95.3 and 80.0%, respectively. The AUC of NAG-1 was 0.912 with its sensitivity and specificity observed to be 76.6 and 79.1%, respectively. In comparison with the high miR-132 expression group and the low NAG-1 mRNA expression group, significantly improved blood biochemistry indexes, sign indexes, blood indexes, and adverse reaction rate were observed among the low miR-132 expression group and the high NAG-1 mRNA expression group. The microRNA.org and luciferase assay revealed NAG-1 to be a target of miR-132. Based on the results of this study, it was concluded that the expressions of MiR-132 and NAG-1 could serve as biological markers in the prediction of the therapeutic efficiency of NSAID treatment in AS patients.

摘要

强直性脊柱炎(AS)是一种常见的慢性风湿性疾病,患有该病的患者体内各种 microRNAs(miRNAs)的表达存在差异,其中一些可能成为新型互补的 AS 生物标志物。在这项研究中,我们招募了 AS 患者,以研究外周血 microRNA-132(miR-132)及其靶基因 NAG-1 的表达与 AS 患者非甾体抗炎药(NSAIDs)治疗临床疗效的相关性。共有 218 例接受口服双氯芬酸钠治疗的 AS 患者,经过 16 周的治疗评估,分为反应组(n=175)和非反应组(n=43)。另外还招募了 113 名健康患者作为研究对象。在第 0、8 和 16 周采集 AS 患者外周血样本,健康患者的相应样本在第 0 周采集。采用 RT-qPCR 检测 miR-132 和 NAG-1 的表达,并通过 ROC 曲线分析外周血 miR-132 表达的诊断价值及其在接受 NSAIDs 治疗的 AS 患者中的预测价值。通过 microRNA.org 和荧光素酶测定验证了 miR-132 和 NAG-1 的靶向关系。与研究中的健康患者相比,治疗前 AS 患者的外周血 miR-132 表达水平更高。治疗前,AS 患者 miR-132 的 ROC 曲线下面积(AUC)为 0.965,临界值为 2.605。miR-132 对 AS 的诊断临床疗效的灵敏度和特异性分别为 91.7%和 97.3%。与非反应组相比,反应组患者的 miR-132 表达水平降低,NAG-1 mRNA 表达水平升高。ROC 结果表明,miR-132 的 AUC 为 0.876,灵敏度和特异性分别为 95.3%和 80.0%。NAG-1 的 AUC 为 0.912,灵敏度和特异性分别为 76.6%和 79.1%。与高 miR-132 表达组和低 NAG-1 mRNA 表达组相比,低 miR-132 表达组和高 NAG-1 mRNA 表达组的血液生化指标、体征指标、血液指标和不良反应发生率均显著改善。microRNA.org 和荧光素酶测定显示 NAG-1 是 miR-132 的靶基因。基于这项研究的结果,我们得出结论,miR-132 和 NAG-1 的表达可以作为预测 AS 患者 NSAIDs 治疗疗效的生物标志物。

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