Aberrant methylation of microRNA-34b/c is a predictive marker of metachronous gastric cancer risk

Abstract

BackgroundMetachronous gastric cancer (GC) can develop after endoscopic resection of GC and cannot be predicted based on clinical signature. Aberrant DNA methylation in noncancerous gastric mucosa is strongly implicated in gastric carcinogenesis and could be a useful biomarker of GC risk. We evaluated the clinical utility of DNA methylation as a biomarker of metachronous GC risk.MethodWe carried out scheduled follow-up endoscopy in 129 patients after curative endoscopic resection of GC. Biopsy specimens were collected from noncancerous mucosa in the gastric antrum and body, after which quantitative methylation analysis of miR-34b/c, SFRP1, SFRP2, SFRP5, DKK2 and DKK3 was carried out using bisulfite pyrosequencing. The utility of the methylation for predicting the risk of metachronous GC development was assessed using Kaplan–Meier and Cox proportional hazards model analyses.ResultsDuring the follow-up period, 17 patients (13 %) developed metachronous GCs. The cumulative incidence of metachronous GC was significantly higher among patients with elevated miR-34b/c, SFRP2 and DKK2 methylation in their gastric body. MiR-34b/c showed the strongest association with the risk of metachronous GC, and the cumulative incidence of metachronous GC was much higher in the high-miR-34b/c-methylation group than the low-methylation group. Multivariate analysis adjusted for age, sex, H. pylori status and pathological findings showed miR-34b/c methylation in gastric body to be an independent predictor of metachronous GC risk.ConclusionOur results suggest that methylation of miR-34b/c in the mucosa of the noncancerous gastric body may be a useful biomarker for predicting the risk of metachronous GC.Electronic supplementary materialThe online version of this article (doi:10.1007/s00535-013-0861-7) contains supplementary material, which is available to authorized users.

Morphologic Characterization of Residual DNA Methylation in the Gastric Mucosa after Helicobacter Pylori Eradication

“…The multivariate analysis showed that atrophic type or intestinal metaplasia was the strong independent risk for DNA methylation after H. pylori eradication. Although DNA hypermethylation might be a risk of gastric cancer regardless of H. pylori infection status [6,[19][20][21], in our study, the most important factor of DNA hypermethylation was magnifying NBI and histologic features. This indicates that the methylation change is closely linked to the magnifying NBI and histologic features within the focal points.…”

Endoscopic features associated with development of metachronous gastric cancer in patients who underwent endoscopic resection followed by Helicobacter pylori eradication

“…Other biomarkers for predicting metachronous cancer development have been reported. Several reports have indicated that assessment of the epigenetic field defect using DNA methylation levels could be used as a predictive marker for metachronous gastric cancer after endoscopic resection . However, this method is not yet practical because of the difficulty of analysis and high cost.…”

Detection and clinical significance of DNA repair gene ERCC8 tag SNPs in gastric cancer

“…Research on the occurrence of malignant cancer induced by aberrant methylation-caused gene disability is a hotspot in the field of genetics (34,35). Individual treatment based on genes will be the main trend in the future, with the interpretation of human genetic maps and advances in genetic disease research.…”