PR001428 (Project)

Description:Neuroblastoma (NB) is the most common extra-cranial malignant tumor in children. Although the survival rate of NB has improved over the years, the outcome of NB still remains unfavorable in a high percentage of cases. Prognosis is currently based on a combination of clinical, histo-pathological and biological features, on which patients are classified in different risk groups and addressed to different treatment protocols. A more accurate risk stratification remains a key point in the study of NB: in particular, the availability of novel prognostic biomarkers of metastatic “high risk” NB at diagnosis could help in improving patient stratification, accurately predicting outcome, relapse or response to treatments and also reducing unnecessary therapies and related toxicities. In this study an HRMS-based approach was applied for the first time to study NB with a goal of developing prognostic biomarkers that could help in improving patient stratification and providing novel therapeutic targets. Starting from an untargeted approach the differences in the metabolomic profiles of localized and metastatic patients were investigated. Key metabolites of metastatic NB were identified through differential expression analysis. Among the metabolites of L-DOPA degradation pathway 3-o-methyldopa (3-O-MD) was selected and analysed in a second cohort of patients using a targeted approach based on liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS).