Cystathionine as a Potential Urinary Marker for Diagnosing and Assessing Pretreatment Risk in Neuroblastoma.
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Urinary homovanillic acid (HVA) and vanillylmandelic acid (VMA) are widely used diagnostic markers for neuroblastoma, but urinary markers for risk assessment prior to invasive biopsy are lacking. We hypothesized that cystathionine (CTN) may be a new neuroblastoma biomarker and evaluated its utility for diagnosis and pretreatment risk assessment. 80 participants provided 202 urine samples: 32 from 32 control participants, 29 from 29 patients with primary neuroblastoma, and 141 from 30 patients with residual tumors, 11 of whom had primary neuroblastoma. Urinary CTN and HVA/VMA concentrations were measured using liquid chromatography/mass spectrometry. The area under the receiver operating characteristic curve (ROC-AUC) was used to evaluate diagnostic and pretreatment risk assessment performance according to the International Neuroblastoma Risk Group (INRG) pretreatment risk classification and the revised 2021 Children's Oncology Group (COG) neuroblastoma risk classification. Associations with prognostic factors were also evaluated. The AUC values for diagnosis were 0.920, 0.903, and 0.946 for HVA, VMA, and CTN, respectively. For pretreatment risk assessment (high-risk versus intermediate- and low-risk, and high- and intermediate-risk versus low-risk) the AUCs according to the INRG classification were 0.576 and 0.578 for HVA, 0.524 and 0.513 for VMA, and 0.852 and 0.708 for CTN, respectively, whereas they were 0.530 and 0.741 for HVA, 0.510 and 0.796 for VMA, and 0.758 and 0.981 for CTN, respectively, according to the COG classification. The values for MYCN status were 0.844 for HVA, 0.844 for VMA, and 0.942 for CTN. CTN may be a useful urinary marker for neuroblastoma diagnosis and pretreatment risk assessment.