Micro architectures of Barrett’s esophagus associated with DNA methylation status

Abstract

Abstract Background: DNA methylation is involved in early carcinogenesis in Esophageal adenocarcinoma (EAC) arising from the Barrett's esophagus (BE), suggesting that DNA methylation might be associated with “field defect” in BE. Since morphologic characterization of “field defect” has important implications, we explored micro architectures of on-neoplastic BE associates with DNA methylation using the magnifying narrow-band imaging (NBI) endoscopy. Methods: Using three different groups of biopsies obtained from non-neoplastic BE from patients without cancer (n=66; N group), with EAC (n=27; ADJ group) and EAC (n=22; T group). Methylation status of five candidate genes (N33, DPYS, SLC16A12, miR124a3, miR34bc) were examined by bisulfite pyrosequencing. The magnifying NBI endoscopic features of non-neoplastic BE was divided into three types: small round holes or slit like structures with uniform subepithelial capillary networks (n=40; Slit/hole, S/H); having dense vessels with ambiguous surface structures (n=15; Vessel, V); clearly demarcated oval or tubulovillous structures with coiled or wavy vessels (n=38; Ridge/Villous, R/V). Results: Methylation levels of all five genes were higher in ADJ and T groups compared to that in N group. In the non-neoplastic BE, V type and R/V type presented higher methylation levels in all five genes compared to S/H type. Multivariate analysis revealed that, the NBI features (V and R/V type) in the non-neoplastic BE was independently associated with higher mean Z score methylation of five genes (odds ratio: 7.61, 95% confidence interval: 2.12-27.3, P<0.0001). Conclusions: Micro architectures of BE visualized by the magnifying NBI endoscopy can predict DNA methylation status associated with “field defect”.