Promoter hypermethylation of Death-associated protein-kinase gene associated with advance stage gastric cancer

Oncol Rep. 2005 May;13(5):937-41.

Abstract

Death-associated protein kinase (DAP-kinase) is a serine/threonine kinase and a positive mediator of apoptosis. Down-regulation of DAP-kinase was associated with increased metastatic potential of tumors. Gene promoter hypermethylation could lead to down-regulation of DAP-kinase. We aimed to investigate the frequency of gene promoter methylation of DAP-kinase in gastric carcinoma (GCA) and assessed its association with clinicopathological features. One hundred and seven cases of gastric carcinoma were examined. The relevant clinical and pathological features, including survival data were reviewed. Methylation status was assessed by methylation-specific PCR (MSP). Seventy-four cases (69.2%) of GCA demonstrated promoter methylation of DAP-kinase. Methylation of DAP-kinase was observed in intestinal, diffuse and mixed type of GCA. It also occurred in similar frequency among antral, body and cardiac gastric cancer. No association between methylation status and age or gender was demonstrated. However, the methylated cases correlated with the presence of nodal metastasis (p=0.041), advance stage of disease (p=0.029) and a poorer event-free survival (log-rank test p=0.0141). DAP-kinase promoter methylation as a potential prognostic marker for gastric cancer patients deserved further evaluation.

MeSH terms

  • Apoptosis Regulatory Proteins
  • Calcium-Calmodulin-Dependent Protein Kinases / genetics*
  • DNA Methylation*
  • DNA Primers
  • DNA, Neoplasm / genetics*
  • DNA, Neoplasm / isolation & purification
  • Death-Associated Protein Kinases
  • Disease-Free Survival
  • Female
  • Genetic Markers
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Polymerase Chain Reaction
  • Promoter Regions, Genetic*
  • Stomach Neoplasms / enzymology
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology*

Substances

  • Apoptosis Regulatory Proteins
  • DNA Primers
  • DNA, Neoplasm
  • Genetic Markers
  • Death-Associated Protein Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases