Hypermethylated DNA as potential biomarkers for gastric cancer diagnosis

Clin Biochem. 2011 Dec;44(17-18):1405-11. doi: 10.1016/j.clinbiochem.2011.09.006. Epub 2011 Sep 16.

Abstract

Objectives: To demonstrate the diagnostic significance of methylation, an important molecular event in gastric carcinogenesis.

Design and methods: We used methylation microarray to determine candidate genes, and performed MSP to evaluate the methylation status of them in tissues and sera. The effect of demethylation on mRNA expression was investigated by rt-PCR after gastric cancer cell lines were treated with 5-Aza-dC for 96 h.

Results: In tissues and sera of gastric cancer patients, a higher prevalence of methylation was observed for BX141696, WT1, CYP26B1, and KCNA4, compared to healthy people (p<0.05, respectively). Detection of the methylation prevalence of KCNA4 and CYP26B1 together in serum demonstrated the good sensitivity (91.3%) and specificity (92.1%). After 5-Aza-dC treatment in gastric cancer cell lines, the mRNA expression level of these genes was restored.

Conclusions: This study underscores the potential application of measurement of serum DNA methylation of these genes, as promising tool for gastric cancer detection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / blood*
  • Biomarkers, Tumor / genetics
  • Carcinoma / diagnosis*
  • Carcinoma / genetics
  • Carcinoma / pathology
  • Case-Control Studies
  • Cell Line, Tumor
  • Cytochrome P-450 Enzyme System / blood
  • Cytochrome P-450 Enzyme System / genetics
  • DNA / blood*
  • DNA / genetics
  • DNA Methylation*
  • Gene Expression
  • Gene Expression Regulation, Neoplastic
  • Genetic Association Studies
  • Humans
  • Kv1.4 Potassium Channel / blood
  • Kv1.4 Potassium Channel / genetics
  • Middle Aged
  • Neoplasm Invasiveness
  • Polymerase Chain Reaction
  • Promoter Regions, Genetic
  • Retinoic Acid 4-Hydroxylase
  • Sensitivity and Specificity
  • Stomach Neoplasms / diagnosis*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / pathology
  • Tissue Array Analysis
  • Young Adult

Substances

  • Biomarkers, Tumor
  • KCNA4 protein, human
  • Kv1.4 Potassium Channel
  • DNA
  • Cytochrome P-450 Enzyme System
  • CYP26B1 protein, human
  • Retinoic Acid 4-Hydroxylase