Plasma exosomal microRNAs are non-invasive biomarkers of moyamoya disease: A pilot study

Highlights

• miRNA-seq analysis obtained 1,002 differentially expressed miRNAs.

• Differentially expressed miRNAs were mainly enriched in axon guidance, regulation of the actin cytoskeleton and the MAPK signaling pathway.

• 10 miRNAs (miR-1306-5p, miR-196b-5p, miR-19a-3p, miR-22-3p, miR-320b, miR-34a-5p, miR-485-3p, miR-489-3p, miR-501-3p, and miR-487-3p) were found to be associated with the most sensitive and specific pathways for MMD prediction.

Abstract

Background

As a progressive cerebrovascular disease, Moyamoya Disease (MMD) is a common cause of stroke in children and adults. However, the early biomarkers and pathogenesis of MMD remain poorly understood.

Methods and material

This study was conducted using plasma exosome samples from MMD patients. Next-generation high-throughput sequencing, real-time quantitative PCR, gene ontology analysis, and Kyoto Encyclopaedia of Genes and Genomes pathway analysis of ideal exosomal miRNAs that could be used as potential biomarkers of MMD were performed. The area under the Receiver Operating Characteristic (ROC) curve was used to evaluate the sensitivity and specificity of biomarkers for predicting events.

Results

Exosomes were successfully isolated and miRNA-sequence analysis yielded 1,002 differentially expressed miRNAs. Functional analysis revealed that they were mainly enriched in axon guidance, regulation of the actin cytoskeleton and the MAPK signaling pathway. Furthermore, 10 miRNAs (miR-1306-5p, miR-196b-5p, miR-19a-3p, miR-22-3p, miR-320b, miR-34a-5p, miR-485-3p, miR-489-3p, miR-501-3p, and miR-487-3p) were found to be associated with the most sensitive and specific pathways for MMD prediction.

Conclusions

Several plasma secretory miRNAs closely related to the development of MMD have been identified, which can be used as biomarkers of MMD and contribute to differentiating MMD from non-MMD patients before digital subtraction angiography.

Keywords
Moyamoya disease; Exosomal microRNA; Actin cytoskeleton signalling pathway; Plasma; Biomarkers