title: GALNT9 gene expression is a prognostic marker in neuroblastoma patients.
abstract: BACKGROUND
  The enzymes encoded by the GALNT [UDP-N-acetyl-α-d-galactosamine:polypeptide N-acetylgalactosaminyltransferase (GALNAC-T)] gene family catalyze the first step of O-glycosylation. Little is known about the link between expression of the genes encoding GALNAC-T enzymes and tumor progression in neuroblastoma, a pediatric cancer that can be classified as either low or high risk. We assessed the expression of genes in the GALNT family in a large cohort of neuroblastoma patients and characterized members of this family that might be used as new prognostic markers.
  
  
  METHODS
  Reverse-transcription PCR analysis of 14 GALNT genes with a panel of neuroblastoma cell lines identified the GALNT9 gene as playing a potential role in disease progression. We used the log-rank test and the multivariable Cox proportional hazards model with a cohort of 122 neuroblastoma patients to analyze the relationship between GALNT9 expression and overall survival or disease-free survival.
  
  
  RESULTS
  In the high-risk neuroblastoma experimental model IGR-N-91, GALNT9 expression was present in neuroblasts derived from primary tumors but not in neuroblasts from metastatic bone marrow. Moreover, GALNT9 in neuroblastoma cell lines was expressed in substrate adherent (S)-type cell lines but not in neuronal (N)-type lines. In the tumor cohort, GALNT9 expression was associated with high overall survival, independent of the standard risk-stratification covariates. GALNT9 expression was significantly associated with disease-free survival for patients currently classified as at low risk (P < 0.0007).
  
  
  CONCLUSIONS
  GALNT9 expression correlates with both improved overall survival in low- and high-risk groups and an improved clinical outcome (overall and disease-free survival) in low-risk patients. Thus, the GALNT9 expression may be a prognostic marker for personalized therapy.
authors.affiliation: Laboratorio de Glicobiología e Inmunología Tumoral, Institut Pasteur de Montevideo, Montevideo, Uruguay. nberois@pasteur.edu.uy
authors.forename: Nora
authors.initials: N
authors.lastname: Berois
authors.forename: Charles-Henry
authors.initials: CH
authors.lastname: Gattolliat
authors.forename: Enrique
authors.initials: E
authors.lastname: Barrios
authors.forename: Laura
authors.initials: L
authors.lastname: Capandeguy
authors.forename: Sétha
authors.initials: S
authors.lastname: Douc-Rasy
authors.forename: Dominique
authors.initials: D
authors.lastname: Valteau-Couanet
authors.forename: Jean
authors.initials: J
authors.lastname: Bénard
authors.forename: Eduardo
authors.initials: E
authors.lastname: Osinaga
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D045744:Cell Line, Tumor; D006801:Humans; D007223:Infant; D017350:N-Acetylgalactosaminyltransferases / Q000235:genetics*; D009447:Neuroblastoma / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; D017350:N-Acetylgalactosaminyltransferases; C580736:GALNT9 protein, human