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

Abstract

Abstract Neuroblastoma (NB) is the most common extracranial solid tumor in children. NB patients with amplification of the MYCN oncogene usually associated with a high risk of recurrence and poor survival. The small extracellular vesicles (sEVs) have potential as novel appropriate noninvasive tumor biomarkers for diagnosis and prognosis. In this study, the differentially expressed microRNAs (DEMs) were determined in plasma-derived sEVs from 168 participants, including 24 children with NB (9 MYCN+ high-risk (HR) patients, 8 MYCN− HR patients and 7 MYCN− intermediate-risk or low-risk (IR/LR) patients) and also 10 healthy controls (HCs) in the discovery stage using miRNA-seq, 87 neuroblastoma children (28 MYCN+ HR patients, 33 MYCN− HR patients and 26 MYCN− IR/LR patients) and 47 HCs during the validation phase. Our results showed that miR-150-5p, miR-142-5p, miR-30b-5p, miR-320a-3p, miR-30b and miR-342-3p were significantly dysregulated in NB samples with the area under the curve (AUC) over 0.8. Additionally, the expression of miR-150-5p and miR-342-3p with the AUC of 0.738 was also significantly different between the MYCN+ group and MYCN− group. Functional analysis demonstrated the key mRNAs and signaling pathways involved in NB and MYCN amplification. In summary, our findings indicated plasma sEVs-derived miRNAs can be used as efficacy diagnosis and prognosis biomarkers in NB.