Hypermethylated DNA as potential biomarkers for gastric cancer diagnosis.

OBJECTIVES:To demonstrate the diagnostic significance of methylation, an important molecular event in gastric carcinogenesis. DESIGN AND METHODS:We 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. RESULTS:In 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. CONCLUSIONS:This study underscores the potential application of measurement of serum DNA methylation of these genes, as promising tool for gastric cancer detection.

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