Exploratory profiling of serum small extracellular vesicle-associated miRNAs as candidate biomarkers for Moyamoya disease
Purpose Moyamoya disease (MMD) is a chronic progressive cerebrovascular disease with elevated rates of mortality and disability in children and adults. Therefore, early and accurate identification of MMD is crucial for good prognosis, effective therapeutics, and increased clinical survival rates. Serum small extracellular vesicles (EVs) have attracted significant attention as innovative liquid biopsy biomarkers for screening and diagnosing MMD. Patients and methods We performed small RNA (sRNA) sequencing to determine the miRNA profiles of serum-derived EVs and integrated the Weighted gene co-expression network analysis to identify the serum exosomal miRNA biomarkers within a screening cohort comprised of 10 adult MMD patients (38.7 ± 12.2 years), along with 10 age and gender-matched healthy controls (adult HCs, 41.0 ± 15.0 years) and 11 pediatric MMD patients (8.6 ± 2.2 years). Results Our results indicated that mRNA-derived fragments represented the largest annotated mapped fraction, whereas miRNAs were the principal small regulatory RNA class further analyzed for candidate biomarker discovery. Among them, specific EV-derived miRNAs, miR-378c, miR-205-5p and miR-374a-5p, were identified as closely related to disease progression in adult MMD patients. This miRNA exhibited significantly altered expression levels in adult MMD patients but not in pediatric cases, suggesting a potential role in the pathophysiology of MMD that might be associated with age-dependent factors or stages of disease development. The findings of this study emphasize the potential application of serum-EV-derived miRNAs as biomarkers for MMD, which could serve as an indicator for disease progression in adult patients. While the profiles of pediatric MMD were less significantly altered, the association of EV-derived miRNAs with adult disease progression presents a promising lead for adult-specific biomarkers. Conclusion These results provide a foundation for larger-scale studies with longitudinal follow-up to validate using serum exosomal miRNAs, particularly miR-205-5p and miR-374a-5p as non-invasive diagnostic and prognostic biomarkers for patients with adult MMD, enhancing clinical management and patient outcomes.