Analysis of promoter methylation, polymorphism and expression profile of cytotoxic T-lymphocyte-associated antigen-4 in patients with gastric cancer

J Gastrointestin Liver Dis. 2014 Sep;23(3):249-53. doi: 10.15403/jgld.2014.1121.233.dmkt.

Abstract

Background and aim: Cytotoxic T lymphocyte-associated antigen-4 (CTLA4) is a crucial immune-checkpoint receptor regulating T-cell activation. The current study was carried out to evaluate the function of CTLA4 gene in patients with gastric cancer.

Methods: The methylation of CTLA4 gene promoter was evaluated by methylation-specific polymerase chain reaction (MSP) technique using 85 paraffin-embedded gastric cancer tissue samples and normal tissue on the tumor margins as control tissue samples. Expression analysis was performed on paraffin-embedded tissue samples (25 each of cancerous and normal tissues) using Real-time PCR.

Results: Statistically significant differences were observed between the tumor and margin-cell areas with respect to promoter methylation status (OR = 4.829, 95% CI: 2.46-9.48, p < 0.001) and CTLA4 expression profile (mean +/- SD = 7.56 +/- 17.35, p = 0.04).

Conclusion: To the best of our knowledge, the current study is the first one highlighting the association between promoter hypermethylation of CTLA4 gene, decreased CTLA4 expression, and increased risk of gastric cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • CTLA-4 Antigen / genetics*
  • DNA Methylation*
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Odds Ratio
  • Paraffin Embedding
  • Phenotype
  • Polymorphism, Genetic*
  • Promoter Regions, Genetic*
  • Real-Time Polymerase Chain Reaction
  • Risk Factors
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / immunology
  • Stomach Neoplasms / pathology
  • Stomach Neoplasms / surgery

Substances

  • CTLA-4 Antigen
  • CTLA4 protein, human