CpG island methylator phenotype and Helicobacter pylori infection associated with gastric cancer

AIM:To investigate the association between the CpG island methylator phenotype(CIMP) and serum Helicobacter pylori(H.pylori) levels for clinical prediction of gastric cancer(GC) progression.METHODS:We analyzed the serum CIMP status of 75 patients with GC using a methylation marker panel and a methylation-specific polymerase chain reaction.Serum samples from 40 healthy persons were examined at the same time.The genes examined were APC,WIF-1,RUNX-3,DLC-1,SFRP-1,DKK and E-cad.H.pylori infection in serum was assayed with an anti-H.pylori immunoglobulin G antibody test and a rapid urease test.RESULTS:The frequencies of high-level methylation in GC tissues for the seven genes were:48% for APC,57.33% for WIF-1,56% for RUNX-3,50.67% for DLC-1,52% for SFRP-1,54.67% for DKK,and 48% for E-cad.The frequencies in GC serum were 30.67% for APC,34.67% for WIF-1,37.33% for RUNX-3,29.33% for DLC-1,33.33% for SFRP-1,32% for DKK,and 26.67% for E-cad.CIMP+(defined as ≥ 3 methylated genes) was associated with 47(62.67%) GC tissue samples and 44(58.67%) GC serum samples.CIMP+ was not associated with non-neoplastic mucosal tissues or the serum of healthy persons.Of the 75 GC cases,51(68%) were H.pylori +,and 24(32%) were H.pylori-.Of the 51 H.pylori + cases,36 were CIMP+ and 15 were CIMP-.In contrast,for the 24 H.pylori-cases,11 were CIMP+,and 13 were CIMP-.The difference was significant between the H.pylori + and H.pylori-groups(χ 2 = 4.27,P < 0.05).Of the 51 H.pylori + GC patients,34 were CIMP+ and 17 were CIMP-,while among the 24 H.pylori-GC cases,10 were CIMP+ and 14 were CIMP-.The difference was significant between the H.pylori+ and H.pylori-groups(χ 2 = 4.21,P < 0.05).A 2-year follow-up showed significant difference in the rates of metastasis and recurrence between H.pylori +/CIMP+ cases and the H.pylori +/CIMP-cases or CIMP-cases associated with H.pylori assayed in serum(P < 0.05).However,there were no significant differences in survival rates between the two groups.CONCLUSION:H.pylori +/CIMP+ cases are associated with higher rates of metastasis and recurrence than H.pylori +/CIMP-cases.Serum may be useful for examining CIMP status.