miRNA 表达谱与肿瘤坏死因子抑制剂治疗类风湿关节炎患者临床应答的相关性：一项前瞻性队列研究。
Correlation of microRNA expression profile with clinical response to tumor necrosis factor inhibitor in treating rheumatoid arthritis patients: A prospective cohort study.
机构信息
Department of Geratology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Oncology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
出版信息
J Clin Lab Anal. 2019 Sep;33(7):e22953. doi: 10.1002/jcla.22953. Epub 2019 Jun 27.
BACKGROUND
This study aimed to explore the correlation of circulating microRNA (miRNA) expression profile with clinical response to tumor necrosis factor (TNF) inhibitor in treating rheumatoid arthritis (RA) patients.
METHODS
Baseline PBMC samples from eight responders and eight non-responders after 24-week TNF inhibitor (etanercept) treatment were subjected to miRNA microarray. Then, top 10 dysregulated miRNAs were selected and further validated by quantitative polymerase chain reaction (qPCR) in baseline PBMC samples from 92 RA patients treated with 24-week TNF inhibitor (etanercept). Responders and non-responders were divided referring to the decline in disease activity score in 28 joints.
RESULTS
In microarray assay, total 59 upregulated and 78 downregulated miRNAs were identified in responders compared to non-responders, which were mainly enriched in regulating immune- and inflammation-related biological processes and pathways. The top 10 dysregulated miRNAs were as follows: miR-192-5p, miR-146a-5p, miR-19b-3p, miR-320c, miR-335-5p, miR-149-3p, miR-766-3p, let-7a-5p, miR-24-3p, and miR-1226-5p. In qPCR validation, miR-146a-5p was increased, while let-7a-5p was decreased in responders compared with non-responders. Multivariate logistic analysis illuminated that miR-146a-5p and CRP independently correlated with higher clinical response, while let-7a-5p and biologics history independently associated with lower clinical response. Subsequently, receiver operating characteristic curve showed that combination of these four independent factors presented with a great predictive value for clinical response with area under curve: 0.863, 95% CI 0.781-0.945.
CONCLUSION
miRNA expression profile is closely implicated in the treatment efficacy of TNF inhibitor, and combined measurement of miR-146a-5p, let-7a-5p, CRP, and biologics history disclosed a great predictive value for clinical response to TNF inhibitor in RA patients.
背景
本研究旨在探讨循环 microRNA（miRNA）表达谱与肿瘤坏死因子（TNF）抑制剂治疗类风湿关节炎（RA）患者的临床反应之间的相关性。
方法
对 8 例接受 24 周 TNF 抑制剂（依那西普）治疗后出现应答和 8 例无应答的患者的基线 PBMC 样本进行 miRNA 微阵列分析。然后，选择前 10 个差异表达的 miRNA，并用 92 例接受 24 周 TNF 抑制剂（依那西普）治疗的 RA 患者的基线 PBMC 样本进行定量聚合酶链反应（qPCR）进一步验证。根据 28 个关节疾病活动评分的下降，将应答者和无应答者分为两组。
结果
在微阵列分析中，与无应答者相比，应答者中总共鉴定出 59 个上调和 78 个下调的 miRNA，这些 miRNA主要富集在调节免疫和炎症相关的生物过程和途径中。前 10 个差异表达的 miRNA 如下：miR-192-5p、miR-146a-5p、miR-19b-3p、miR-320c、miR-335-5p、miR-149-3p、miR-766-3p、let-7a-5p、miR-24-3p 和 miR-1226-5p。在 qPCR 验证中，与无应答者相比，应答者中 miR-146a-5p 增加，而 let-7a-5p 减少。多变量 logistic 分析表明，miR-146a-5p 和 CRP 与较高的临床反应独立相关，而 let-7a-5p 和生物制剂病史与较低的临床反应独立相关。随后，受试者工作特征曲线显示，这四个独立因素的组合具有较高的预测价值，曲线下面积为 0.863，95%置信区间为 0.781-0.945。
结论
miRNA 表达谱与 TNF 抑制剂的治疗效果密切相关，miR-146a-5p、let-7a-5p、CRP 和生物制剂病史的联合测量对 RA 患者 TNF 抑制剂的临床反应具有很好的预测价值。
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