Abstract 4450: Silencing NKD2 by promoter region hypermethylation promotes esophageal cancer progression by activating Wnt signaling

Background: Despite the use of surgery or chemoradiotherapy to treat, esophageal cancer, its prognosis still remains poor, with a 5-year survival below 15%. Recent insights into the epigenetic mechanisms associated with multi-step carcinogenesis provide new opportunities to develop novel effective targeted therapies for esophageal squamous cell carcinoma. Naked cuticle homolog 2 (NKD2) was found frequently methylated in human breast cancer. The epigenetic changes and mechanisms of NKD2 in human esophageal cancer remain unclear. Methods: Nine esophageal cancer cell lines and 154 cases of primary esophageal cancer samples were analyzed using methylation specific PCR, immunohistochemistry, western blot, flow cytometry techniques and a xenograft mouse model. Results: Loss of NKD2 expression and complete methylation were found in KYSE150 and TE1 cells. Reduced expression and partial methylation were observed in KYSE30, KYSE70, KYSE410, KYSE140 and COLO680 cells. High level expression and unmethylation were detected in KYSE450 and TE8 cells. Re-expression of NKD2 was induced by 5-aza-2’-deoxycytidine in NKD2 unexpressed or reduced cells. NKD2 was methylated in 53.2% (82/154) of human primary esophageal cancer samples, and promoter region hypermethylation was associated with reduced expression of NKD2 significantly (p