title: Low expression of N-myc downstream-regulated gene 2 (NDRG2) correlates with poor prognosis in hepatoblastoma.
abstract: OBJECTIVE
  Despite tremendous progress in therapy, about 30% of patients with hepatoblastoma still succumb to the disease. Thus, the development of improved therapies as well as the identification of prognostic factors are urgently needed.
  
  
  METHODS
  In the present study, expression and promoter methylation of the N-myc downstream-regulated gene (NDRG2), a tumor suppressor gene contributing to the regulation of the Wnt signalling pathway, was analysed in 38 hepatoblastoma samples by real-time reverse transcription-PCR and pyrosequencing, respectively.
  
  
  RESULTS
  The NDRG2 gene was highly expressed in normal pediatric liver tissue, but was significantly downregulated in heptoblastoma primary tumors. Detailed methylation analysis of CpG sites in the NDRG2 promoter region revealed a general high degree of DNA methylation in hepatoblastoma, which correlated with the suppression of NDRG2. By analyzing clinicopathological features we could demonstrate a strong association between low NDRG2 expression and tumor metastasis. Importantly, the overall survival analysis by Kaplan-Meier revealed that high NDRG2 expression was correlated with a higher survival rate in hepatoblastoma patients.
  
  
  CONCLUSIONS
  Our data show that downregulation of NDRG2 may play an important role in advanced hepatoblastomas.
authors.affiliation: Department of Pediatric Surgery, Dr. von Hauner Children's Hospital, Ludwig-Maximilians-University Munich, Lindwurmstr. 2a, 80337, Munich, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Gödeke
authors.affiliation: Department of Pediatric Surgery, Dr. von Hauner Children's Hospital, Ludwig-Maximilians-University Munich, Lindwurmstr. 2a, 80337, Munich, Germany.
authors.forename: Elke
authors.initials: E
authors.lastname: Luxenburger
authors.affiliation: Department of Pediatric Surgery, Dr. von Hauner Children's Hospital, Ludwig-Maximilians-University Munich, Lindwurmstr. 2a, 80337, Munich, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Trippel
authors.affiliation: Department of Pediatric Surgery, Dr. von Hauner Children's Hospital, Ludwig-Maximilians-University Munich, Lindwurmstr. 2a, 80337, Munich, Germany.
authors.forename: Kristina
authors.initials: K
authors.lastname: Becker
authors.affiliation: Department of Pediatric Surgery, Dr. von Hauner Children's Hospital, Ludwig-Maximilians-University Munich, Lindwurmstr. 2a, 80337, Munich, Germany.
authors.forename: Beate
authors.initials: B
authors.lastname: Häberle
authors.affiliation: Institute of Pathology, Ludwig-Maximilians-University Munich, Thalkirchner Str. 36, 80337, Munich, Germany.
authors.forename: Josef
authors.initials: J
authors.lastname: Müller-Höcker
authors.affiliation: Department of Pediatric Surgery, Dr. von Hauner Children's Hospital, Ludwig-Maximilians-University Munich, Lindwurmstr. 2a, 80337, Munich, Germany.
authors.forename: Dietrich
authors.initials: D
authors.lastname: von Schweinitz
authors.affiliation: Department of Pediatric Surgery, Dr. von Hauner Children's Hospital, Ludwig-Maximilians-University Munich, Lindwurmstr. 2a, 80337, Munich, Germany. roland.kappler@med.uni-muenchen.de.
authors.forename: Roland
authors.initials: R
authors.lastname: Kappler
mesh_terms: D002648:Child; D002675:Child, Preschool; D019175:DNA Methylation; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018197:Hepatoblastoma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007223:Infant; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D009362:Neoplasm Metastasis; D011379:Prognosis; D011401:Promoter Regions, Genetic; D016019:Survival Analysis; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: C466228:NDRG2 protein, human; D025521:Tumor Suppressor Proteins
keywords: Expression; Hepatoblastoma; Methylation; N-myc downstream-regulated gene 2; Prognosis; Pyrosequencing