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Use of Capillary Electrophoresis Immunoassay to Search for Potential Biomarkers of Amyotrophic Lateral Sclerosis in Human Platelets
Published on: February 10, 2020
Insights from meta-analysis and experimental validation identify exosomal miR-146a-5p as a potential biomarker for
Anjali Rawat1, Shiffali Khurana1,2, Sagar Verma1,3,4
1Department of Biotechnology and Research, Sir Ganga Ram Hospital, Delhi, 110060, India.
Abstract:
MicroRNAs (miRNAs) have emerged as key regulators in the pathogenesis of amyotrophic lateral sclerosis (ALS). Despite growing evidence that miRNAs exhibit altered expression profiles in ALS, their utility as a biomarker remains limited. To address this, we conducted a meta-analysis using the Robust Rank Aggregation package, incorporating 20 differential miRNA profiling studies. Among these, miR-146a-5p emerged as the most dysregulated and significant miRNA in ALS (P = 0.0000142, P-adj = 0.0096), particularly in extracellular vesicle-derived studies. To evaluate its diagnostic accuracy, we validated miR-146a-5p expression in serum-derived exosomes and observed a significant increase in sporadic ALS (sALS) patients (n = 22) as compared to healthy controls (n = 18). Moreover, higher levels of miR-146a-5p were strongly associated with longer survival (≥ 5 years) (P = 0.0135), with a positive correlation between miR-146a-5p expression and survival duration (P = 0.0313) in sALS patients. Further, gene set enrichment analysis of miR-146a-5p target genes highlighted critical involvement of the Immune system and NF-kappa B signaling pathways in ALS pathophysiology. These findings highlight miR-146a-5p as a potential biomarker for ALS.
Insights
MicroRNAs (miRNAs) are key in amyotrophic lateral sclerosis (ALS). This study identifies miR-146a-5p as a significant biomarker in ALS patients, showing altered levels and association with longer survival.
Area of Science:
- Neuroscience
- Molecular Biology
- Biomarker Discovery
Background:
- MicroRNAs (miRNAs) play a crucial role in the pathogenesis of amyotrophic lateral sclerosis (ALS).
- Altered miRNA expression is observed in ALS, but their diagnostic utility is limited.
- Identifying reliable miRNA biomarkers is essential for ALS diagnosis and prognosis.
Purpose of the Study:
- To identify significant miRNAs associated with ALS through meta-analysis.
- To evaluate the diagnostic accuracy of candidate miRNAs, specifically miR-146a-5p.
- To explore the correlation between miR-146a-5p levels, survival, and underlying biological pathways in ALS.
Main Methods:
- A meta-analysis of 20 differential miRNA profiling studies was performed using Robust Rank Aggregation.
- miR-146a-5p expression was validated in serum-derived exosomes from sporadic ALS (sALS) patients and healthy controls.
- Gene set enrichment analysis was conducted on miR-146a-5p target genes.
Main Results:
- miR-146a-5p was identified as the most significantly dysregulated miRNA in ALS.
- Elevated miR-146a-5p levels were observed in sALS patients compared to controls.
- Higher miR-146a-5p expression correlated with longer survival in sALS patients.
- Immune system and NF-kappa B signaling pathways were implicated through miR-146a-5p target analysis.
Conclusions:
- miR-146a-5p is a promising and significant biomarker for amyotrophic lateral sclerosis (ALS).
- Its expression levels are associated with disease status and patient survival.
- miR-146a-5p may play a role in ALS pathophysiology via immune and NF-kappa B signaling.

