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

Abstract

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. 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. 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). 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.