Multiple sclerosis: microRNA expression profiles accurately differentiate patients with relapsing-remitting disease from healthy controls.
Multiple sclerosis: microRNA expression profiles accurately differentiate patients with relapsing-remitting disease from healthy controls.
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DOI：
10.1371/journal.pone.0007440
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发表时间：
2009-10-13
期刊：
影响因子：
3.7
通讯作者：
Meese E
中科院分区：
文献类型：
--
作者：
Keller A;Leidinger P;Lange J;Borries A;Schroers H;Scheffler M;Lenhof HP;Ruprecht K;Meese E
多发性硬化症(MS)是一种慢性中枢神经系统炎症性脱髓鞘疾病，其临床表现和治疗反应具有异质性。识别生物标志物似乎是改善MS诊断以及监测疾病活动性和治疗反应的理想选择。MicroRNAs(MiRNAs)是一种短的非编码RNA，已被证明有可能作为不同人类疾病的生物标记物，最明显的是癌症。在这里，我们分析了866个人类miRNAs的表达谱。我们利用人类miRNA芯片和Geniom Real Time Analyzer(GRTA)平台，详细研究了20例复发-缓解期MS(RRMS)患者和19例健康对照血细胞中miRNA的表达。我们确定了165个在RRMS患者中显著上调或下调的miRNAs，与健康对照组相比。单项miRNA标记hsa-miR-145对MS的特异性为89.5%，敏感性为90.0%，准确性为89.7%。用径向基函数核支持向量机对48个miRNAs进行10倍交叉验证，其特异度为95%，敏感度为97.6%，准确度为96.3%。虽然在MS患者中，165个miRNAs中有43个以前与其他人类疾病有关，但到目前为止，其余122个miRNAs仅与MS相关。我们的研究具有两方面的意义。血细胞中miRNA的表达谱可作为MS的生物标志物，miRNA表达异常可能在MS的发病机制中起一定作用。
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system, which is heterogenous with respect to clinical manifestations and response to therapy. Identification of biomarkers appears desirable for an improved diagnosis of MS as well as for monitoring of disease activity and treatment response. MicroRNAs (miRNAs) are short non-coding RNAs, which have been shown to have the potential to serve as biomarkers for different human diseases, most notably cancer. Here, we analyzed the expression profiles of 866 human miRNAs. In detail, we investigated the miRNA expression in blood cells of 20 patients with relapsing-remitting MS (RRMS) and 19 healthy controls using a human miRNA microarray and the Geniom Real Time Analyzer (GRTA) platform. We identified 165 miRNAs that were significantly up- or downregulated in patients with RRMS as compared to healthy controls. The best single miRNA marker, hsa-miR-145, allowed discriminating MS from controls with a specificity of 89.5%, a sensitivity of 90.0%, and an accuracy of 89.7%. A set of 48 miRNAs that was evaluated by radial basis function kernel support vector machines and 10-fold cross validation yielded a specificity of 95%, a sensitivity of 97.6%, and an accuracy of 96.3%. While 43 of the 165 miRNAs deregulated in patients with MS have previously been related to other human diseases, the remaining 122 miRNAs are so far exclusively associated with MS. The implications of our study are twofold. The miRNA expression profiles in blood cells may serve as a biomarker for MS, and deregulation of miRNA expression may play a role in the pathogenesis of MS.
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