A novel molecular marker for early detection and evaluating prognosis of gastric cancer: N-myc downstream regulated gene-1 (NDRG1)

Scand J Gastroenterol. 2010 Aug;45(7-8):898-908. doi: 10.3109/00365520903242580.

Abstract

Objective: N-myc downstream regulated gene-1 (NDRG1) is known as a differentiation-related gene that plays important roles in cell differentiation, organ formation, and embryonic development. NDRG1 was recently found to significantly down regulate in a variety of different neoplasms. Its significance in gastric cancer has not been studied.

Materials and methods: NDRG1 was detected at its protein level by immunohistochemistry in formalin-fixed and paraffin-embedded sections with a total of 110 pair gastric cancer specimens including tumor and corresponding paraneoplastic tissues; NDRG1 mRNA was detected by real time-polymerase chain reaction. Meanwhile, the correlations between NDRG1 and clinicopathological factors were observed. Overexpression of NDRG1 has influence on the biological behavior of gastric cancer cell, which was detected by cell growth assay, apoptosis assay, and in vitro motility and invasion assay.

Results: NDRG1 protein was down regulated in gastric cancer tissues, and the NDRG1 low expression rate was 73.6% (79/110). Moreover, NDRG1 expression has a significant inverse correlation with tumor stromal invasion, lymph node metastasis, pathological stage, but not with distant metastasis. The patients with low NDRG1 expression had a significantly shorter survival opportunity than those with high NDRG1 expression. In addition, overexpression of NDRG1 induced early apoptosis and inhibited SGC7901 cell proliferation and its motility and invasion capability.

Conclusions: NDRG1 plays a significant role in carcinogenesis and preventing the metastasis and invasion of gastric cancer cells. NDRG1 could be developed as a marker contributing to diagnosis and evaluating prognosis in gastric cancer, as well as a potential therapeutic target of gastric cancer.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers
  • Cell Cycle Proteins / metabolism*
  • Down-Regulation*
  • Female
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Male
  • Middle Aged
  • Prognosis
  • Stomach Neoplasms / diagnosis*
  • Stomach Neoplasms / genetics*

Substances

  • Biomarkers
  • Cell Cycle Proteins
  • Intracellular Signaling Peptides and Proteins
  • N-myc downstream-regulated gene 1 protein