Parkinsons Disease-related Circulating microRNA Biomarkers——a Validation Study

David Petillo; Stephen Orey; Aik Choon Tan; Lars Forsgren; Sok Kean Khoo; David Petillo; Stephen Orey; Aik Choon Tan; Lars Forsgren; Sok Kean Khoo

doi:10.3934/medsci.2015.1.7

AIMS Medical Science

2015, Volume 2, Issue 1: 7-14. doi: 10.3934/medsci.2015.1.7

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Research article Special Issues

Parkinsons Disease-related Circulating microRNA Biomarkers——a Validation Study

1.
Molecular Diagnostics Program, College of Health Professions, Ferris State University, Grand Rapids, MI 49503, USA;
2.
Department of Cell and Molecular Biology, Grand Valley State University, Grand Rapids, MI 49503, USA;
3.
School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA;
4.
Department of Pharmacology and Clinical Neuroscience, Umeå University, SE-901 87 Umeå, Sweden

Received: 06 February 2014 Accepted: 04 February 2015 Published: 06 February 2015

Parkinson's disease (PD) is the second most common neurodegenerative disease. One of the major challenges in studying this progressive neurological disorder is to identify and develop biomarkers for early detection. Recently, several blood-based microRNA (miRNA) biomarkers for PD have been reported. However, follow-up studies with new, independent cohorts have been rare. Previously, we identified a panel of four circulating miRNA biomarkers for PD (miR-1826, miR-450b-3p, miR-505, and miR-626) with biomarker performance of 91% sensitivity and 100% specificity. However, the expression of miR-450b-3p could not be detected in a new, independent validation set. In our current study, we improved the detection power by including a non-biased pre-amplification step in quantitative real-time PCR (qRT-PCR) and reevaluated the biomarker performance. We found the panel of four PD-related miRNAs achieved the predictive power of 83% sensitivity and 75% specificity in our validation set. This is the first biomarker validation study of PD which showed reproducibility and robustness of plasma-based circulating miRNAs as molecular biomarkers and qRT-PCR as potential diagnostic assay.

Keywords:

Citation: David Petillo, Stephen Orey, Aik Choon Tan, Lars Forsgren, Sok Kean Khoo. Parkinsons Disease-related Circulating microRNA Biomarkers——a Validation Study[J]. AIMS Medical Science, 2015, 2(1): 7-14. doi: 10.3934/medsci.2015.1.7

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Abstract

Table 1. Characteristics of study subjects for PD biomarker validation set.

	PD	Healthy Controls	PSP	MSA
PD = Parkinson’s disease; PSP = progressive supranuclear palsy; MSA = multiple system atrophy; M = Male; F = Female
Sample size Age Hoehn & Yahr	16 M 14 F 69.4 ± 9.0 2.2 ± 0.7	3 M 4 F 72.3± 3.4	2 M 3 F 75.2 ± 8.8 4 ± 1.2	2 M 2 F 72.5 ± 17.8 4.5 ± 1.0

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Table 2. Average ΔΔC_T in log2 fold change for miRNA-1826, miR-450b-3_p, miR-505, and miR-626.

	CTR	MSA	PSP
PD = Parkinson’s disease; CTR = healthy controls; MSA = multiple system atrophy; PSP =progressive supranuclear palsy
PD miR-1826 miR-450b-3_p miR-505 miR-626	2.046 −9.355 −1.260 0.326	1.055 −2.857 1.316 5.125	−1.613 −1.920 −1.067 3.918
MSA miR-1826 miR-450b-3_p miR-505 miR-626	1.939 −3.274 −1.659 −15.698		−1.702 1.488 −1.405 −1.308
PSP	miR-1826 miR-450b-3 miR-505 miR-626	3.300 −4.874 −1.181 −12.000

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Figure 1. miRNA expression levels of circulating miR-1826 in healthy controls (CTR), Parkinson’s disease (PD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP) patients. * Statistically significance between groups (P < 0.05).

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Figure 2.miRNA expression levels of circulating miR-450b-3_p in healthy controls (CTR), Parkinson’s disease (PD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP) patients. * Statistically significance between groups (P < 0.05).

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Figure 3.miRNA expression levels of circulating miR-505 in healthy controls (CTR), Parkinson’s disease (PD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP) patients.

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Figure 4.miRNA expression levels of circulating miR-626 in healthy controls (CTR), Parkinson’s disease (PD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP) patients.

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