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.