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Suppressed expression of NDRG2 correlates with poor prognosis in pancreatic cancer

Akihiro Yamamura1, Koh Miura, Hideaki Karasawa

  • 1Department of Surgery, Tohoku University, Graduate School of Medicine, Sendai, Japan; Department of Pathology, Tohoku University, Graduate School of Medicine, Sendai, Japan.

Biochemical and Biophysical Research Communications
|October 19, 2013
PubMed

Insights

N-myc downstream regulated gene 2 (NDRG2) is downregulated in pancreatic cancer, correlating with poor prognosis. Histone modification, not DNA methylation, appears to silence NDRG2, suggesting its potential as a therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Genetics

Background:

  • Pancreatic cancer is a lethal disease with poorly understood molecular mechanisms.
  • N-myc downstream regulated gene 2 (NDRG2) is a potential tumor suppressor frequently downregulated in pancreatic cancer.
  • Limited data exists on NDRG2 expression in resected pancreatic cancer tissues.

Purpose of the Study:

  • To investigate the association between NDRG2 expression and prognosis in pancreatic cancer.
  • To explore the role of epigenetic mechanisms, specifically DNA methylation and histone modification, in NDRG2 regulation.
  • To determine if NDRG2 expression is an independent prognostic factor.

Main Methods:

  • Immunohistochemistry was used to assess NDRG2 expression in 69 surgically resected pancreatic cancer specimens.
  • Cell lines were treated with trichostatin A (histone deacetylase inhibitor) and 5-aza-2' deoxycytidine (DNA demethylating agent).
  • Methylation-specific PCR was performed to detect hypermethylation in cell lines and tissues.

Main Results:

  • NDRG2-negative staining was significantly associated with poor prognosis in pancreatic cancer patients (P=0.038).
  • Trichostatin A upregulated NDRG2 expression in low-expressing cell lines, while 5-aza-2' deoxycytidine had no significant effect.
  • No hypermethylation of NDRG2 was detected in pancreatic cancer cell lines or specimens.

Conclusions:

  • NDRG2 functions as a tumor suppressor gene in pancreatic carcinogenesis.
  • Epigenetic silencing of NDRG2 likely involves histone modifications rather than DNA methylation.
  • NDRG2 expression serves as an independent prognostic factor for pancreatic cancer.
Keywords:
5-aza-2′ deoxycytidine5-aza-dCAUB2MEpigenetic silencingHDACHypermethylationMSPN-myc downstream regulated gene 2NDRG2Pancreatic cancerPrognostic factorTSAarbitrary unitcDNAcomplementary DNAhistone deacetylasemethylation-specific PCRqRT-PCRquantitative reverse transcription polymerase chain reactiontrichostatin Aβ2-microglobulin

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