Extracellular vesicle derived miRNAs from plasma as promising diagnosis and prognosis biomarkers for neuroblastoma.

Neuroblastoma (NB) is the most common extracranial solid tumor in children. MYCN amplification remains a critical indicator of high-risk disease and poor prognosis. Small extracellular vesicles (sEVs) carry microRNAs (miRNAs) with promising diagnostic potential. This study identified plasma sEV-derived miRNA biomarkers for NB diagnosis and MYCN status prediction. Using miRNA-seq, we analyzed plasma sEVs from 24 patients with NB (stratified by MYCN status and risk) and 10 healthy controls. Validation was performed in an independent cohort of 87 patients with NB and 47 controls. We identified six miRNAs (miR-150-5p, miR-142-5p, miR-30b-5p, miR-320a-3p, miR-30b, and miR-342-3p) that were significantly dysregulated in patients with NB, all showing excellent diagnostic accuracy (AUC >0.8). Notably, miR-150-5p and miR-342-3p differentiated MYCN-amplified from nonamplified patients (AUC = 0.738). Functional analysis revealed involvement in key NB pathways. Our findings demonstrate that plasma sEV-derived miRNAs represent valuable noninvasive biomarkers for neuroblastoma diagnosis and risk stratification.