外泌体 miRNA 作为帕金森病和进行性核上性麻痹的外周生物标志物：一项初步研究。

Exosomal miRNA as peripheral biomarkers in Parkinson's disease and progressive supranuclear palsy: A pilot study.

机构信息

Institute of Molecular Bioimaging and Physiology (IBFM), National Research Council (CNR), Section of Germaneto, 88100, Catanzaro, Italy.

Institute of Neurology, Department of Medical and Surgical Sciences, University "Magna Graecia", Germaneto, 88100, Catanzaro, Italy.

出版信息

Parkinsonism Relat Disord. 2021 Dec;93:77-84. doi: 10.1016/j.parkreldis.2021.11.020. Epub 2021 Nov 24.

DOI:10.1016/j.parkreldis.2021.11.020

PMID:34839044

Abstract

INTRODUCTION

Parkinson's disease (PD), a progressive neurodegenerative disease, can be misdiagnosed with atypical conditions such as Progressive Supranuclear Paralysis (PSP) due to overlapping clinical features. MicroRNAs (miRNAs) are small non-coding RNAs with a key role in post-transcriptional gene regulation. The aim was to identify a set of differential exosomal miRNAs biomarkers, which may aid in diagnosis.

METHODS

We analyzed the serum level of 188 miRNAs in a discovery set, by using RTqPCR based TaqMan assay, in a small cohort of healthy controls, PD and PSP patients. Subsequently, the differentially expressed miRNAs, between PSP and PD patients, were further tested in a larger and independent cohort of 33 healthy controls, 40 PD and 20 PSP patients. The most accurate diagnostic exosomal miRNAs classifiers were identified in a logistic regression model.

RESULTS

A statistically significant set of three exosomal miRNAs: miR-21-3p, miR-22-3p and miR-223-5p, discriminated PD from HC (area under the curve of 0.75), and a set of three exosomal miRNAs, miR-425-5p, miR-21-3p, and miR-199a-5p, discriminated PSP from PD with good diagnostic accuracy (area under the curve of 0.86). Finally, the classifier that best discriminated PSP from PD consisted of six exosomal miRNAs (area under the curve = 0.91), with diagnostic sensitivity and specificity of 0.89 and 0.90, respectively.

CONCLUSIONS

Based on our analysis, these data showed that exosomal miRNAs could act as biomarkers to differentiate between PSP and PD.

摘要

简介

帕金森病（PD）是一种进行性神经退行性疾病，由于重叠的临床特征，可能会误诊为不典型疾病，如进行性核上性麻痹（PSP）。微小 RNA（miRNA）是一种小的非编码 RNA，在转录后基因调控中起着关键作用。本研究旨在鉴定一组差异表达的外泌体 miRNA 生物标志物，以辅助诊断。

方法

我们通过基于 RTqPCR 的 TaqMan 检测分析了发现组中 188 种 miRNA 的血清水平，该组由小队列的健康对照者、PD 和 PSP 患者组成。随后，在由 33 名健康对照者、40 名 PD 和 20 名 PSP 患者组成的更大、独立的队列中，进一步检测了 PSP 和 PD 患者之间差异表达的 miRNA。通过逻辑回归模型鉴定最准确的诊断性外泌体 miRNA 分类器。

结果

一组统计学上显著的三个外泌体 miRNA（miR-21-3p、miR-22-3p 和 miR-223-5p）区分了 PD 与 HC（曲线下面积为 0.75），一组三个外泌体 miRNA（miR-425-5p、miR-21-3p 和 miR-199a-5p）可较好地区分 PSP 与 PD（曲线下面积为 0.86）。最后，最佳区分 PSP 与 PD 的分类器由六个外泌体 miRNA 组成（曲线下面积=0.91），诊断敏感性和特异性分别为 0.89 和 0.90。