PT - JOURNAL ARTICLE AU - Fjoralba Zeka AU - Alan Van Goethem AU - Katrien Vanderheyden AU - Fleur Demuynck AU - Tim Lammens AU - Anneleen Decock AU - Hetty H Helsmoortel AU - Joëlle Vermeulen AU - Rosa Noguera AU - Ana P Berbegall AU - Valérie Combaret AU - Gudrun Schleiermacher AU - Geneviève Laureys AU - Alexander Schramm AU - Johannes H Schulte AU - Sven Rahmann AU - Julie Bienertová-Vašků AU - Pavel Mazánek AU - Marta Jeison AU - Shifra Ash AU - Michael D Hogarty AU - Mirthala Moreno-Smith AU - Eveline Barbieri AU - Jason Shohet AU - Frank Berthold AU - Frank Speleman AU - Matthias Fischer AU - Katleen De Preter AU - Pieter Mestdagh AU - Jo Vandesompele TI - Circulating microRNA biomarkers for metastatic disease in neuroblastoma patients AID - 10.1101/309823 DP - 2018 Jan 01 TA - bioRxiv PG - 309823 4099 - http://biorxiv.org/content/early/2018/04/27/309823.short 4100 - http://biorxiv.org/content/early/2018/04/27/309823.full AB - In this study, the circulating miRNome from diagnostic neuroblastoma serum was assessed for identification of non-invasive biomarkers with potential in monitoring metastatic disease. After determining the circulating neuroblastoma miRNome, 743 miRNAs were screened in two 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 expression 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, suggesting this miRNA signature may be applied to monitor disease burden.