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Cancers (Basel). 2019 Sep 30;11(10). pii: E1476. doi: 10.3390/cancers11101476.

Exosomal microRNAs from Longitudinal Liquid Biopsies for the Prediction of Response to Induction Chemotherapy in High-Risk Neuroblastoma Patients: A Proof of Concept SIOPEN Study.

Author information

1
Laboratorio di Biologia Molecolare, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy. martinamorini@gaslini.org.
2
Laboratorio di Biologia Molecolare, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy.
3
U.O.C. Laboratorio di Cellule Staminali Post Natali e Terapie Cellulari, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy.
4
Dipartimento di Oncoematologia, Ospedale Pediatrico Bambino Gesù IRCCS, 00165 Roma, Italy.
5
Hospital Universitario y Politècnico La Fe, 46026 Valencia, Spain.
6
Leeds Institute of Medical Research at St James's University Hospital, LS9 7TF Leeds, UK.
7
Laboratorio Terapie Sperimentali in Oncologia, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy.
8
Anatomia Patologica, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy.
9
Curie Institute, 75248 Paris, France.
10
St Anna Children's Hospital, 1090 Wien, Austria.
11
Oncoematologia Pediatrica, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy.
12
Fondazione IRCSS Istituto Nazionale dei Tumori, 20133 Milano, Italy.
13
Laboratorio di Biologia Molecolare, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy. mariacarlabosco@gaslini.org.

Abstract

Despite intensive treatment, 50% of children with high-risk neuroblastoma (HR-NB) succumb to their disease. Progression through current trials evaluating the efficacy of new treatments for children with HR disease usually depends on an inadequate response to induction chemotherapy, assessed using imaging modalities. In this study, we sought to identify circulating biomarkers that might be detected in a simple blood sample to predict patient response to induction chemotherapy. Since exosomes released by tumor cells can drive tumor growth and chemoresistance, we tested the hypothesis that exosomal microRNA (exo-miRNAs) in blood might predict response to induction chemotherapy. The exo-miRNAs expression profile in plasma samples collected from children treated in HR-NBL-1/SIOPEN before and after induction chemotherapy was compared to identify a three exo-miRs signature that could discriminate between poor and good responders. Exo-miRNAs expression also provided a chemoresistance index predicting the good or poor prognosis of HR-NB patients.

KEYWORDS:

chemotherapy response; exosomes; liquid biopsy; miRNA; neuroblastoma

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