Exo-miRNAs expression provides a chemoresistance index predicting prognosis of high-risk neuroblastoma patients

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.

Researchers at the Istituto Giannina Gaslini 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, they 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.

Chemoresistance Index differentiating good and poor responders


K-means clustering built on the CI. The algorithm identifies two groups of patients: cluster 1 includes subjects showing high CI toward CBDCA, CDDP, and DOXO and low CI for VP-16 and VCR; cluster 2 contains patients showing opposite features, with low CI toward CBDCA, CDDP, and DOXO and slightly high CI to VP-16 and VCR. Event-free survival (EFS) defined the response to induction chemotherapy: patients that reported a relapse, a progression, or died are addressed as poor responders. The association between the identified clusters and EFS is significant (p value < 0.03), showing that the CI is indicative of a poor response.

Morini M, Cangelosi D, Segalerba D, Marimpietri D, Raggi F, Castellano A, Fruci D, de Mora JF, Cañete A, Yáñez Y, Viprey V, Corrias MV, Carlini B, Pezzolo A, Schleiermacher G, Mazzocco K, Ladenstein R, Sementa AR, Conte M, Garaventa A, Burchill S, Luksch R, Bosco MC, Eva A, Varesio L. (2019) 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 (Basel) 11(10). [article]

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