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Low expression of N-myc downstream-regulated gene 2 (NDRG2) correlates with poor prognosis in hepatoblastoma

Hepatology International volume 10, pages 370–376 (2016)Cite this article

Abstract

Background/Purpose of the study

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.

Conclusion

Our data show that downregulation of NDRG2 may play an important role in advanced hepatoblastomas.

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Abbreviations

HB:

Hepatoblastoma

HCC:

Hepatocellular carcinoma

CTNNB1:

Catenin beta 1

NDRG2:

N-myc downstream-regulated gene 2

SIOPEL:

Childhood liver tumors strategy group

GPOH:

Society for pediatric oncology and haematology

LTR:

Liver tumor registry

RT-PCR:

Quantitative real-time PCR

TBP:

TATA-Box-binding-protein

CpG:

Cytosine-phospho-guanine

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Acknowledgements

This work was supported by grants from the Friedrich Baur Foundation, Munich, Germany (to J.G.), the Bettina Bräu foundation, Munich, Germany and the Gänseblümchen-Voerde foundation, Voerde, Germany (to R.K.). We are grateful to Fatemeh Promoli for technical assistance.

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Affiliations

  1. Department of Pediatric Surgery, Dr. von Hauner Children’s Hospital, Ludwig-Maximilians-University Munich, Lindwurmstr. 2a, 80337, Munich, Germany

    Jan Gödeke, Elke Luxenburger, Franziska Trippel, Kristina Becker, Beate Häberle, Dietrich von Schweinitz & Roland Kappler

  2. Institute of Pathology, Ludwig-Maximilians-University Munich, Thalkirchner Str. 36, 80337, Munich, Germany

    Josef Müller-Höcker

Authors
  1. Jan Gödeke
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  2. Elke Luxenburger
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  3. Franziska Trippel
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  4. Kristina Becker
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  5. Beate Häberle
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  6. Josef Müller-Höcker
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  7. Dietrich von Schweinitz
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  8. Roland Kappler
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Corresponding author

Correspondence to Roland Kappler.

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Conflict of interest

Jan Gödeke, Elke Luxenburger, Franziska Trippel, Kristina Becker, Beate Häberle, Josef Müller-Höcker, Dietrich von Schweinitz and Roland Kappler declare that they have no conflicts of interest.

Ethical standards

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (Institutional and National) and with the Helsinki Declaration of 1975, as revised in 2008. This study was reviewed and approved by the ethics committee of the Medical Faculty at the University of Munich, Germany. All samples were taken with informed consent of the donor’s parents.

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Gödeke, J., Luxenburger, E., Trippel, F. et al. Low expression of N-myc downstream-regulated gene 2 (NDRG2) correlates with poor prognosis in hepatoblastoma. Hepatol Int 10, 370–376 (2016). https://doi.org/10.1007/s12072-015-9686-1

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  • DOI: https://doi.org/10.1007/s12072-015-9686-1

Keywords

  • Hepatoblastoma
  • N-myc downstream-regulated gene 2
  • Prognosis
  • Pyrosequencing
  • Methylation
  • Expression