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Published on: February 12, 2018
Plasma-based circulating MicroRNA biomarkers for Parkinson's disease
Sok Kean Khoo1, David Petillo, Un Jung Kang
1Center for Neurodegenerative Science, Van Andel Institute, Grand Rapids, MI 49503, USA. Kean.Khoo@vai.org
Background:
The current "gold-standard" for Parkinson's disease (PD) diagnosis is based primarily on subjective clinical rating scales related with motor features. Molecular biomarkers that are objective and quantifiable remain attractive as clinical tools to detect PD prior to its motor onsets.
Objective:
Here, we aimed to identify, develop, and validate plasma-based circulating microRNA (miRNAs) as biomarkers for PD.
Methods:
Global miRNA expressions were acquired from a discovery set of 32 PD/32 controls using microarrays. k-Top Scoring Pairs (k-TSP) algorithm and significance analysis of microarrays (SAM) were applied to obtain comprehensive panels of PD-predictive biomarkers. TaqMan miRNA-specific real-time PCR assays were performed to validate the microarray data and to evaluate the biomarker performance using a new replication set of 42 PD/30 controls. Data was analyzed in a paired PD-control fashion. The validation set was composed of 30 PD, 5 progressive supranuclear palsy, and 4 multiple system atrophy samples from a new clinical site.
Results:
We identified 9 pairs of PD-predictive classifiers using k-TSP analysis and 13 most differentially-expressed miRNAs by SAM. A combination of both data sets produced a panel of PD-predictive biomarkers: k-TSP1 (miR-1826/miR-450b-3p), miR-626, and miR-505, and achieved the highest predictive power of 91% sensitivity, 100% specificity, 100% positive predicted value, and 88% negative predicted value in the replication set. However, low predictive values were shown in the validation set.
Conclusions:
This proof-of-concept study demonstrates the feasibility of using plasma-based circulating miRNAs as biomarkers for neurodegenerative disorders such as PD and shows the challenges of molecular biomarker research using samples from multiple clinical sites.
Insights
Researchers identified plasma microRNAs (miRNAs) as potential biomarkers for Parkinson's disease (PD). While promising in initial tests, their predictive value varied across different clinical sites, highlighting challenges in multi-site biomarker validation.
Area of Science:
- Neuroscience
- Biomarker Discovery
- Genetics
Background:
- Current Parkinson's disease (PD) diagnosis relies on subjective motor assessments.
- Objective, quantifiable molecular biomarkers are needed for early PD detection.
- Plasma-based circulating microRNAs (miRNAs) show potential as diagnostic tools.
Purpose of the Study:
- To identify, develop, and validate plasma-based circulating miRNAs as PD biomarkers.
- To assess the diagnostic potential of miRNA panels in Parkinson's disease.
Main Methods:
- Microarray analysis of miRNA expression in 32 PD patients and 32 controls.
- Utilized k-Top Scoring Pairs (k-TSP) algorithm and Significance Analysis of Microarrays (SAM).
- Validated findings using real-time PCR in a replication set (42 PD/30 controls) and a validation set (30 PD/5 PSP/4 MSA).
Main Results:
- Identified 9 PD-predictive miRNA pairs (k-TSP) and 13 differentially-expressed miRNAs (SAM).
- A combined panel (k-TSP1, miR-626, miR-505) achieved 91% sensitivity and 100% specificity in the replication set.
- Lower predictive values were observed in the multi-site validation set.
Conclusions:
- Plasma-based circulating miRNAs are feasible biomarkers for neurodegenerative disorders like PD.
- This study highlights the challenges in molecular biomarker research across multiple clinical sites.
- Further research is needed to overcome variability in multi-site biomarker validation.
Related Concept Videos
01:24Parkinson Disease l: Introduction
01:24Parkinson Disease ll: Pathophysiology