| Literature DB >> 30518699 |
Fjoralba Zeka1,2, Anneleen Decock1,2, Alan Van Goethem1,2, Katrien Vanderheyden1,2, Fleur Demuynck1, Tim Lammens2,3, Hetty H Helsmoortel1,2, Joëlle Vermeulen4, Rosa Noguera5, Ana P Berbegall5,6, Valérie Combaret7, Gudrun Schleiermacher8, Geneviève Laureys2,3, Alexander Schramm9, Johannes H Schulte9,10,11, Sven Rahmann12, Julie Bienertová-Vašků13, Pavel Mazánek13, Marta Jeison14, Shifra Ash14, Michael D Hogarty15, Mirthala Moreno-Smith16, Eveline Barbieri16, Jason Shohet16, Frank Berthold17, Tom Van Maerken1,2, Frank Speleman1,2, Matthias Fischer17,18, Katleen De Preter1,2, Pieter Mestdagh1,2, Jo Vandesompele1,2.
Abstract
In this study, the circulating miRNome from diagnostic neuroblastoma serum was assessed for identification of noninvasive biomarkers with potential in monitoring metastatic disease. After determining the circulating neuroblastoma miRNome, 743 miRNAs were screened in 2 independent cohorts of 131 and 54 patients. Evaluation of serum miRNA variance in a model testing for tumor stage, MYCN status, age at diagnosis, and overall survival revealed tumor stage as the most significant factor impacting miRNA abundance in neuroblastoma serum. Differential abundance analysis between patients with metastatic and localized disease revealed 9 miRNAs strongly associated with metastatic stage 4 disease in both patient cohorts. Increasing levels of these miRNAs were also observed in serum from xenografted mice bearing human neuroblastoma tumors. Moreover, murine serum miRNA levels were strongly associated with tumor volume. These findings were validated in longitudinal serum samples from metastatic neuroblastoma patients, where the 9 miRNAs were associated with disease burden and treatment response.Entities:
Keywords: Genetics; Noncoding RNAs; Oncology
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Year: 2018 PMID： 30518699 PMCID： PMC6328024 DOI： 10.1172/jci.insight.97021
Source DB: PubMed Journal: JCI Insight ISSN： 2379-3708