Urinary 3-Methoxytyramine Is a Biomarker for MYC Activity in Patients With Neuroblastoma.
JCO Precis Oncol
; 6: e2000447, 2022 01.
Article
in En
| MEDLINE
| ID: mdl-35085004
ABSTRACT
PURPOSE:
Elevated urinary 3-methoxytyramine (3MT) level at diagnosis was recently put forward as independent risk factor for poor prognosis in neuroblastoma. Here, we investigated the biologic basis underlying the putative association between elevated 3MT levels and poor prognosis.METHODS:
Urinary 3MT levels and prognosis were investigated in both retrospective Italian (N = 90) and prospective Dutch (N = 95) cohorts. From the Dutch Cancer Oncology Group cohort (N = 122), patients with available urinary 3MT and gene expression data (n = 90) were used to generate a 3MT gene signature. The 3MT gene signature score was then used to predict survival outcome in the Children's Oncology Group (N = 247) and German Pediatric Oncology Group (N = 498) cohorts and compared with other known gene signatures. Immunohistochemistry of MYCN and dopamine ß-hydroxylase proteins was performed on primary tumors.RESULTS:
Elevated urinary 3MT levels were associated with poor prognosis in a retrospective cohort and a prospective cohort. Moreover, elevated urinary 3MT levels were associated with eight differentially expressed genes, providing a 3MT gene signature that successfully predicted poor clinical outcome. Even among low-risk patients, high 3MT signature score was associated with poor 5-year overall survival (72% v 99% among low-risk patients with a low 3MT signature score), and the 3MT signature score was correlated with MYC activity in the tumor (R = 82%, P < .0001). Finally, a strong MYCN and weak dopamine ß-hydroxylase staining of tumors derived from patients with elevated urinary 3MT levels was observed, linking MYC activity in the tumor to both catecholamine biosynthesis and elevated urinary 3MT levels.CONCLUSION:
Elevated urinary 3MT is a promising biomarker for poor prognosis and reflects increased MYC activity in the tumor. Therefore, urinary 3MT levels should be measured at diagnosis and may assist in assessing risk.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Dopamine
/
Biomarkers, Tumor
/
N-Myc Proto-Oncogene Protein
/
Neuroblastoma
Type of study:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
JCO Precis Oncol
Year:
2022
Document type:
Article
Affiliation country:
Netherlands
Publication country:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
/
US
/
USA