Kong Ruina, Gao Jie, Si Yanhui, Zhao Dongbao
Department of Rheumatology & Immunology, Changhai Hospital, Second Military Medical UniversityShanghai 200433, China.
Department of Surgery, Shanghai Public Health Clinical Center Affiliated to Fudan UniversityShanghai 200433, China.
Am J Transl Res. 2017 Jun 15;9(6):2852-2864. eCollection 2017.
The aim of this study was to investigate the association of circulating miRNAs profile with the risk of knee osteoarthritis (OA), and evaluate their correlation with clinical characteristics. This study was divided into two parts: exploration stage and validation stage. In exploration stage, 8 knee OA patients and 8 age and gender highly matched health controls (HCs) were recruited, and plasma sample were collected for microarray examination. Differentially expressed miRNAs and enrichment analysis were subsequently performed. In validation stage, 100 knee OA patients and 100 age and gender matched HCs were enrolled, and Top 8 differentially expressed miRNAs in microarray were selected for further validation by qPCR. In exploration stage, 41 up-regulated miRNAs and 29 down-regulated miRNAs were identified by microarray, and enrichment analysis disclosed these miRNAs were involved in inflammation- and immunity- related process. Top 8 differentially expressed miRNAs in microarray were determined in the validation stage, and miR-19b-3p, miR-92a-3p, miR-122-5p, miR-486-5p and miR-320b expression were increased in knee OA. Univariate and multivariate logistic analysis showed only miR-19b-3p, miR-122-5p and miR-486-5p were independent factors for knee OA risk, and ROC curve showed combination of miR-19b-3p, miR-122-5p and miR-486-5p has a great diagnostic value for knee OA. Besides, miR-19b-3p and miR-486-5p positively correlates with disease severity. This study revealed that circulating miRNA profiles played a key role in knee OA diagnosis, and combined measurement of miR-19b-3p, miR-122-5p and miR-486-5p could be served as a novel and promising biomarker for diagnosis and disease severity of knee OA.
本研究旨在探讨循环miRNA谱与膝关节骨关节炎(OA)风险的关联,并评估其与临床特征的相关性。本研究分为两个部分:探索阶段和验证阶段。在探索阶段,招募了8例膝关节OA患者和8例年龄、性别高度匹配的健康对照(HCs),并采集血浆样本进行微阵列检测。随后进行差异表达miRNA和富集分析。在验证阶段,纳入100例膝关节OA患者和100例年龄、性别匹配的HCs,并选择微阵列中差异表达排名前8的miRNA通过qPCR进行进一步验证。在探索阶段,通过微阵列鉴定出41个上调的miRNA和29个下调的miRNA,富集分析显示这些miRNA参与炎症和免疫相关过程。在验证阶段确定了微阵列中差异表达排名前8的miRNA,膝关节OA中miR-19b-3p、miR-92a-3p、miR-122-5p、miR-486-5p和miR-320b表达增加。单因素和多因素逻辑分析显示,只有miR-19b-3p、miR-122-5p和miR-486-5p是膝关节OA风险的独立因素,ROC曲线显示miR-19b-3p、miR-122-5p和miR-486-5p联合对膝关节OA具有很大的诊断价值。此外,miR-19b-3p和miR-486-5p与疾病严重程度呈正相关。本研究表明,循环miRNA谱在膝关节OA诊断中起关键作用,联合检测miR-19b-3p、miR-122-5p和miR-486-5p可作为膝关节OA诊断和疾病严重程度的一种新型且有前景的生物标志物。