Urinary biomarkers for monitoring treatment response in neuroblastoma patients.

e22008 Background: Neuroblastoma is the most common extracranial solid tumor in children. Its heterogeneity may account for the non-uniform response to therapy; thus, accurate predictive biomarkers are required. We focused on urinary biomarkers since urine contains numerous low molecular weight metabolites that can be used as reliable and non-invasive biomarkers. We detected more than 2,000 metabolites by liquid chromatography-mass spectrometry (LC-MS) through a comprehensive analysis of metabolites in urine samples of patients with neuroblastoma and identified potential urinary biomarker candidates using the Wilcoxon rank-sum test and random forest. In this study, the levels of urinary biomarker candidates were compared between the responder and resistant groups to identify urinary biomarkers for monitoring treatment response. Furthermore, their effectiveness was compared with minimal residual disease (MRD) markers, which are currently considered to predict tumor relapse. Methods: Thirty-two patients with neuroblastoma were divided into two groups according to their responsiveness to therapy: the responder group, in which patients had no recurrence (60 urine samples from 24 patients) and the resistant group in which patients had a recurrence or died (18 urine samples from 8 patients). Levels of urinary metabolites (homovanillic acid [HVA], vanillylmandelic acid [VMA], 3-methoxytyramine sulfate [3-MTS], vanillactic acid [VLA], 3-methoxytyrosine [3-MTR]), and MRD markers (TH, PHOX2B, MK) were compared between the two groups during treatment. Results: The levels of five urinary metabolites (HVA, VMA, VLA, 3-MTR, 3-MTS) were significantly increased in the resistant group compared to that in the responder group. Conclusions: This study shows that three novel urinary metabolites (VLA, 3-MTR, 3-MTS) are significantly associated with the recurrence or death from neuroblastoma.