A 9-microRNA Signature in Serum Serves as a Noninvasive Biomarker in Early Diagnosis of Alzheimer's Disease
A 9-microRNA Signature in Serum Serves as a Noninvasive Biomarker in Early Diagnosis of Alzheimer's Disease
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DOI：
10.3233/jad-170343
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发表时间：
2017-01-01
影响因子：
4
通讯作者：
Lu, Zhiming
中科院分区：
文献类型：
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作者：
Guo, Rui;Fan, Gang;Lu, Zhiming
阿尔茨海默病（AD）是最常见的年龄相关神经退行性疾病;然而，现在还没有可靠的生物标志物或非侵入性技术可用于其早期检测。最近的研究表明，microRNA（miRNAs）的循环水平谱有可能被用作诊断，分期和各种疾病的进展监测的有价值的生物标志物。在这里，我们报告了一种新的9-miRNA签名（hsa-miR-26 a-5 p，hsa-miR-181 c-3 p，hsa-miR-126- 5 p，hsa-miR-22- 3 p，hsa-miR-148 b-5 p，hsa-miR-106 b-3 p，hsa-miR-6119- 5 p，hsa-miR-1246和hsa-miR-660- 5 p），可以用作检测AD的生物标志物。我们采用下一代测序技术（NGS）分别对19例AD患者和9例健康对照者的血清miRNAs进行了分析。通过定量实时聚合酶链反应（qRT-PCR）对121例AD和86例HC病例的较大队列进行了NGS结果验证。根据简易精神状态检查量表（MMSE）和临床痴呆评定量表（CDR）将所有患者分为轻度、中度和重度AD组。我们的研究表明，不同的血清miRNAs的异常表达发生在AD的不同阶段。AD和HC之间的受试者工作特征曲线下面积（AUC）的差异在70%和85%之间。在9种miRNAs中，hsa-miR-22- 3 p的敏感性和特异性最高，分别为81.8%和70.9%。miRNA-panel对AD的诊断更有价值。提示血清miRNAs的差异表达可作为生物标志物用于AD的早期诊断和临床分期。
Alzheimer's disease (AD) is the most common type of age-related neurodegenerative disorder; nevertheless, nowadays there are no reliable biomarkers or non-invasive techniques available for its early detection. Recent studies have indicated that the circulating level profiles of microRNAs (miRNAs) have the potential to be used as valuable biomarkers for diagnosis, staging, and progress monitoring of various diseases. Here we report a novel 9-miRNA signature (hsa-miR-26a-5p, hsa-miR-181c-3p, hsa-miR-126-5p, hsa-miR-22-3p, hsa-miR-148b-5p, hsa-miR-106b-3p, hsa-miR-6119-5p, hsa-miR-1246, and hsa-miR-660-5p) that can be utilized as biomarker for detecting AD. We respectively profiled the serum miRNAs from 19 AD patients and 9 healthy control (HC) participants using the Next-Generation Sequencing (NGS). The NGS results were validated by quantitative real-time polymerase chain reaction (qRT-PCR) on a larger cohort of 121 AD and 86 HC cases. All the patients were divided into three groups (mild, moderate, and severe AD) based on the Mini-Mental State Examination (MMSE) and Clinical Dementia Rating (CDR). Our research indicates that abnormal expression of distinct serum miRNAs occurs at different stages of AD. The difference of the area under the receiver operator characteristics curve (AUC) between the AD and the HC is between 70% and 85%. Among the 9 miRNAs, hsa-miR-22-3p has the best sensitivity (81.8%) and specificity (70.9%). The miRNA-panel is more valuable for AD diagnosis. The data suggest that the differentially expressed serum miRNAs could be used as biomarkers to improve the diagnosis of AD, particularly at the early stage, and to classify its clinical stages.