利用下一代测序技术验证阿尔茨海默病 microRNAs。

Validating Alzheimer's disease micro RNAs using next-generation sequencing.

机构信息

Clinical Bioinformatics, Saarland University, Saarbrücken, Germany.

出版信息

Alzheimers Dement. 2016 May;12(5):565-76. doi: 10.1016/j.jalz.2015.12.012. Epub 2016 Jan 22.

DOI:10.1016/j.jalz.2015.12.012

PMID:26806387

Abstract

INTRODUCTION

Molecular biomarkers for Alzheimer's disease (AD) can support detection and improved care for patients, but novel candidates require verification. We previously reported a 12-micro RNA (miRNA) blood-based signature using next-generation sequencing (NGS) of 54 AD cases and 22 controls.

METHODS

We performed validation of 49 AD cases and 55 controls using NGS and also included 20 mild cognitive impairment and 90 multiple sclerosis samples to identify nonspecific markers. Thus, 103 AD cases, 77 unaffected controls, and 110 diseased controls were sequenced. Although the initial cohort came predominantly from the United States, the validation samples were collected in Germany.

RESULTS

Five hundred eighty miRNAs were detected in the blood. In the initial cohort, we observed 203, in the validation cohort, 146 dysregulated miRNAs at a significance level of 0.05. With 68 miRNAs, the overlap was significant (P = .0003). Likewise, the area under the receiver operator characteristic curve values of the miRNAs correlated (correlation of 0.93; 95% confidence interval 0.89-0.96; P <10(-16)).

DISCUSSION

MiRNAs have the potential to support AD diagnosis and patient care.

摘要

简介

阿尔茨海默病（AD）的分子生物标志物可用于支持 AD 患者的检测和改善护理，但需要对新的候选标志物进行验证。我们之前曾使用下一代测序（NGS）对 54 例 AD 病例和 22 例对照进行了一个包含 12 个 microRNA（miRNA）的血液标志物研究。

方法

我们使用 NGS 对 49 例 AD 病例和 55 例对照进行了验证，并纳入了 20 例轻度认知障碍和 90 例多发性硬化症样本以识别非特异性标志物。因此，对 103 例 AD 病例、77 例无 AD 对照和 110 例疾病对照进行了测序。尽管最初的队列主要来自美国，但验证样本是在德国收集的。

结果

在血液中检测到 580 个 miRNA。在最初的队列中，我们观察到了 203 个失调的 miRNA，在验证队列中，有 146 个 miRNA 在 0.05 的显著水平上失调。有 68 个 miRNA 的重叠是显著的（P = 0.0003）。同样，miRNA 的接收器操作特征曲线下面积值也存在相关性（相关性为 0.93；95%置信区间为 0.89-0.96；P <10(-16)）。