Hypermethylated DNA as potential biomarkers for gastric cancer diagnosis

ObjectivesTo demonstrate the diagnostic significance of methylation, an important molecular event in gastric carcinogenesis.Design and methodsWe 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.ResultsIn 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.ConclusionsThis study underscores the potential application of measurement of serum DNA methylation of these genes, as promising tool for gastric cancer detection.

► We find some previously unreported genes through Methylation DNA Microarray.
► The association of the methylation status of these 4 genes with GC has never before been reported.
► Good concordance between tumor and serum DNA methylation has been shown for WT1, KCNA4, and CYP26B1.
► Detection of methylation status in serum for KCNA4 and CYP26B1 shows good sensitivity and specificity.