CpG Island Methylator Phenotype in Primary Gastric Carcinoma

Abstract

Gastric cancers (GC) with methylation of multiple CpG islands have a CpG island methylator phenotype (CIMP) and they can have different biological features. The aim of this study was to investigate the DNA methylation status of GCs and its association with their clinicopathological features. We evaluated the methylation status of four genes (MINT1, MINT2, MINT25 and MINT31) in 105 primary GCs using bisulfite-pyrosequencing analysis. We classified tumors as CIMP-high (CIMP-H), CIMP-low (CIMP-L) or CIMP-negative (CIMP-N) based on the methylation of MINT1, MINT2, MINT25, and MINT31. Overall, the prevalence of CIMP-H, CIMP-L and CIMP-N was 22% (23/105), 52% (55/105) and 26% (27/105), respectively. We observed a significant difference in tumor stage (stages I-II vs. stages III-IV) between CIMP-H and CIMP-N tumors (P = 0.0435). No significant differences were observed in clinicopathological characteristics (gender, age, location and tumor differentiation) among the CIMP phenotypes. The prognoses of patients with a CIMP-H tumor is likely to be better than those with CIMP-L or CIMP-N tumors, but these differences are not statistically significant (P = 0.074 and P = 0.200). Our results suggest that CIMP may define a subgroup of GCs with distinct biological features.