Extracellular vesicles-derived miR-760 and miR-98-5p as differentiating biomarkers for MS phenotypes

ABSTRACT: Objective. Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system with heterogenous clinical course, lacking non-invasive biomarkers for early phenotype differentiation. This study aimed to identi-fy circulating extracellular vesicle (EV)-derived miRNA signatures and as-sociated disease-specific molecular markers capable of distinguishing stable relapsing-remitting MS (RRMS) from secondary progressive MS (SPMS). Materials and methods. Plasma samples were collected from patients with stable RRMS, SPMS, and healthy controls (HC), followed by EVs isolation and characterization using transmission electron microscopy, dynamic light scattering, and flow cytometry. RNA was extracted from EVs, and miRNA profiles were ana-lyzed via RNA sequencing and RT-qPCR. Cytokine and neurodegeneration marker levels were quantified using the BioPlex® multiplex system and ELISA. Functional enrichment and network analyses of miRNA targets were performed, alongside logistic regression modeling to assess diagnostic utility. Results. Four EV-derived miRNAs (miR-760, miR-98-5p, miR-301a-3p, and miR-223-3p) showed significant differences between stable RRMS and SPMS. The integrative model incorporating these miRNAs with FGF basic protein achieved excellent discrimination between MS phenotypes (AUC = 0.97). Moreover, miR-760 emerged as the most robust predictive biomarker for stable RRMS classification. In turn, miR-98-5p showed the highest up-regulation in both stable RRMS and SPMS relative to HC. miRNA targets network analysis further revealed distinct immunoregulatory patterns for stable RRMS and SPMS. Conclusions. Plasma-derived EV-miRNAs, particularly miR-760 and miR-98-5p, showed strong potential as non-invasive biomarkers for stable RRMS and SPMS phenotypes. Integrating EV-miRNA profiling with protein bi-omarkers enhances diagnostic precision and may support personalized management strategies in MS.

ORGANISM(S): Homo sapiens

PROVIDER: GSE303912 | GEO | 2026/02/11

REPOSITORIES: GEO