Perfetti Alessandra, Greco Simona, Bugiardini Enrico, Cardani Rosanna, Gaia Paola, Gaetano Carlo, Meola Giovanni, Martelli Fabio
Policlinico San Donato-IRCCS, San Donato Milanese, Milan, Italy.
Policlinico San Donato-IRCCS, San Donato Milanese, Milan, Italy; University of Milan, Milan, Italy.
Neuromuscul Disord. 2014 Jun;24(6):509-15. doi: 10.1016/j.nmd.2014.02.005. Epub 2014 Feb 18.
Myotonic dystrophy type 1 (DM1) lacks non-invasive and easy to measure biomarkers, still largely relying on semi-quantitative tests for diagnostic and prognostic purposes. Muscle biopsies provide valuable data, but their use is limited by their invasiveness. microRNA (miRNAs) are small non-coding RNAs regulating gene expression that are also present in biological fluids and may serve as diseases biomarkers. Thus, we tested plasma miRNAs in the blood of 36 DM1 patients and 36 controls. First, a wide miRNA panel was profiled in a patient subset, followed by validation using all recruited subjects. We identified a signature of nine deregulated miRNAs in DM1 patients: eight miRNAs were increased (miR-133a, miR-193b, miR-191, miR-140-3p, miR-454, miR-574, miR-885-5p, miR-886-3p) and one (miR-27b) was decreased. Next, the levels of these miRNAs were used to calculate a "DM1-miRNAs score". We found that both miR-133a levels and DM1-miRNAs score discriminated DM1 from controls significantly and Receiver-Operator Characteristic curves displayed an area under the curve of 0.94 and 0.97, respectively. Interestingly, both miR-133a levels and DM1-miRNAs score displayed an inverse correlation with skeletal muscle strength and displayed higher values in more compromised patients. In conclusion, we identified a characteristic plasma miRNA signature of DM1. Although preliminary, this study indicates miRNAs as potential DM1 humoral biomarkers.
1型强直性肌营养不良（DM1）缺乏非侵入性且易于测量的生物标志物，目前在很大程度上仍依赖半定量检测进行诊断和预后评估。肌肉活检可提供有价值的数据，但其应用因具有侵入性而受到限制。微小RNA（miRNA）是一类调控基因表达的小型非编码RNA，也存在于生物体液中，可能作为疾病的生物标志物。因此，我们检测了36例DM1患者和36例对照者血液中的血浆miRNA。首先，在一部分患者中对广泛的miRNA谱进行了分析，随后使用所有招募的受试者进行验证。我们在DM1患者中鉴定出9种失调miRNA的特征：8种miRNA上调（miR-133a、miR-193b、miR-191、miR-140-3p、miR-454、miR-574、miR-885-5p、miR-886-3p），1种（miR-27b）下调。接下来，利用这些miRNA的水平计算出一个“DM1-miRNA评分”。我们发现，miR-133a水平和DM1-miRNA评分均能显著区分DM1患者与对照者，受试者工作特征曲线下面积分别为0.94和0.97。有趣的是，miR-133a水平和DM1-miRNA评分均与骨骼肌力量呈负相关，且在病情更严重的患者中值更高。总之，我们鉴定出了DM1特征性的血浆miRNA特征。尽管本研究尚处于初步阶段，但表明miRNA作为潜在的DM1体液生物标志物。
