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Open AccessArticle

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

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Laboratorio di Biologia Molecolare, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy
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U.O.C. Laboratorio di Cellule Staminali Post Natali e Terapie Cellulari, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy
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Dipartimento di Oncoematologia, Ospedale Pediatrico Bambino Gesù IRCCS, 00165 Roma, Italy
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Hospital Universitario y Politècnico La Fe, 46026 Valencia, Spain
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Leeds Institute of Medical Research at St James’s University Hospital, Leeds LS9 7TF, UK
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Laboratorio Terapie Sperimentali in Oncologia, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy
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Anatomia Patologica, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy
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Curie Institute, 75248 Paris, France
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St. Anna Children’s Hospital and Children’s Cancer Research Institute (CCRI), Department of Paediatrics, Medical University, 1090 Vienna, Austria
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Oncoematologia Pediatrica, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy
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Fondazione IRCSS Istituto Nazionale dei Tumori, 20133 Milano, Italy
*
Authors to whom correspondence should be addressed.
The authors contributed equally to this work.
Deceased.
§
The authors share senior authorship.
The authors dedicate this article to the memory of Luigi Varesio, highly brilliant and inspiring scientist who, during the course of this study, passed away.
Cancers 2019, 11(10), 1476; https://doi.org/10.3390/cancers11101476
Received: 9 August 2019 / Revised: 10 September 2019 / Accepted: 26 September 2019 / Published: 30 September 2019
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. View Full-Text
Keywords: neuroblastoma; exosomes; chemotherapy response; miRNA; liquid biopsy neuroblastoma; exosomes; chemotherapy response; miRNA; liquid biopsy
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Morini, M.; Cangelosi, D.; Segalerba, D.; Marimpietri, D.; Raggi, F.; Castellano, A.; Fruci, D.; Font de Mora, J.; Cañete, A.; Yáñez, Y.; Viprey, V.; Corrias, M.V.; Carlini, B.; Pezzolo, A.; Schleiermacher, G.; Mazzocco, K.; Ladenstein, R.; Sementa, A.R.; Conte, M.; Garaventa, A.; Burchill, S.; Luksch, R.; Bosco, M.C.; Eva, A.; Varesio, L. 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 . Cancers 2019, 11, 1476.

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