Hypermethylation-modulated down-regulation of CDH1 expression contributes to the progression of esophageal cancer

摘要: CDH1, a cell adhesion molecule, which plays key role in maintaining the epithelial phenotype, is regarded as an invasion-suppressor gene light of accumulating evidence from vitro experiments and clinical observations. In attempt to clarify mechanism responsible for inactivation this carcinomas, we investigated methylation status CDH1 5'-CpG islands its regulatory progression esophageal squamous carcinoma. Real-time methylation-specific polymerase chain reaction (qMSP) treatment with demethylating agent 5-aza-2'-deoxycytidine (5-Aza-CdR) were conducted analyze at promoter region human carcinoma lines, EC1 EC9706. A total 235 invasive carcinomas (ESCC) stages I-IV their corresponding normal tissue samples, included immunohistochemistry study analysis CDH1. The results demonstrate that EC9706 cells, methylated 5-Aza-CdR restored expression. Enhanced expression decreased migration, invasion ability increased ability. Decreased was detected 59.6% ESCC tissues, compared adjacent non-neoplastic epithelia, had close correlation primary tumor status, lymph node distant metatasis clinicopathologic stage. Hypermethylation 97.9% 140 cases low promoters (P=0.929) closely correlated lack proteins. Cox regression model survival showed increases greater impact on prognosis than These findings suggest silencing by hypermethylation resultant reduction may play important ESCC. significant predictor patients after surgery.