外周血miR-200c-3p、miR-99b-5p和miR-150-5p作为缺血性脑卒中生物标记物的研究

Peripheral blood miR-200c-3p, miR-99b-5p and miR-150-5p as biomarkers for ischemic stroke

目的 探讨外周全血miR-200c-3p、miR-15b-5p、miR-99b-5p和miR-150-5p表达水平与缺血性脑卒中（IS）发生的关联性,以及其作为IS生物标记物的可行性. 方法 选择45例2013年7月至11月在深圳市人民医院确诊的IS初发病例,以及45例与之年龄性别相匹配的在同地区社区健康服务中心做常规健康体检的对照,采用实时定量PCR检测外周全血miR-200c-3p、miR-15b-5p、miR-99b-5p和miR-150-5p的表达水平,多元Logistic回归分析miRNA表达水平与缺IS发生的关联,受试者工作特征曲线（ROC）分析miRNA是否可作为判断IS的依据. 结果 IS病例外周血miR-200c-3p和miR-15b-5p表达水平显著高于对照,而miR-99b-5p和miR-150-5p表达水平显著低于对照者,差异均有统计学意义（P＜0.05）.miR-200c-3p、miR-99b-5p和miR-150-5p与IS发生具有显著关联[OR值和95％CI分别为6.30 （1.46～27.20）、0.10 （0.02～0.43）和0.06（0.01～0.30）;P值分别为0.014、0.002、0.001].与传统危险因素模型相比,加入单个或2个以上miRNA都可以显著增加曲线下面积且差异有统计学意义（P＜0.05）. 结论 miR-200c-3p、miR-99b-5p和miR-150-5p的表达水平与IS发生具有显著关联,有望作为IS的生物标记物.

Objective To investigate the association between expression levels of peripheral blood miR-200c-3p,miR-15b-5p,miR-99b-5p and miR-150-5p and occurrence of ischemic stroke （IS）,and to explore if these miRNAs can be biomarkers for IS.Methods Forty-five newly-diagnosed IS patients enrolled in our hospital from July to November 2013 and 45 age-and gender-matched controls from physical examination in the community health center were chosen in our study;the expression levels of whole blood miR-200c-3p,miR-15b-5p,miR-99b-5p and miR-150-5p were detected by real-time quantitative-PCR.Multivariate Logistic regression analysis was applied to evaluate the associations between miRNA expression levels and occurrence of IS.The receiver operating characteristic curve （ROC） analysis was conducted to assess the performance ofmiRNAs as biomarker for IS.Results As compared with those in the controls,the expression levels ofmiR-200c-3p and miR-15b-5p in IS patients were significantly higher,while miR-99b-5p and miR-150-5p expression levels in IS patients were significantly lower （P〈0.05）.The expression levels of miR-200c-3p,miR-99b-5p and miR-150-5p were significantly associated with the occurrence of IS （adjusted odds ratio [OR]：6.30,95% confidence interval [CI]：1.46-27.20 and P=0.014;OR：0.10,95%CI：0.02-0.43 and P=0.002;OR：0.06,95%CI：0.01-0.30 and P=0.001,respectively）.Results of the ROC analysis showed that addition of one miRNA or miRNA panels to traditional risk factors led to significant improvement in the area under the curve （P〈0.05）.Conclusion The expression levels of miR-200c-3p,miR-99b-5p and miR-150-5p are significantly associated with the occurrence of IS,and have potential as biomarkers for IS.