Identification of as an epigenetically regulated tumor suppressor and biomarker for malignant phenotypes of squamous cell carcinoma of the esophagus.

The poor prognosis and increasing incidence of esophageal squamous cell carcinoma (ESCC) highlight the need for identification of novel ESCC-associated molecular events to improve the diagnosis, and treatment of this disease. Non-specific cytotoxic cell receptor protein 1 () was reported to be abundantly expressed in human squamous epithelium and to be involved in cell proliferation; however, the role of in ESCC remains unclear. To elucidate the oncological roles of in ESCC, expression, DNA methylation, and copy numbers were analyzed in ESCC cell lines. Nine ESCC cell lines demonstrated different mRNA expression levels and all exhibited hypermethylation of the promoter, but no copy number loss. Additionally, expression was determined in 213 surgically resected esophageal tissue samples. mRNA expression levels were reduced in ESCC tissues compared with corresponding non-cancerous adjacent tissues in 204 (95.8%) patients. Patients in the low expression group tended to have a higher recurrence rate and a shorter overall survival time compared with those in the high expression group. Additionally, multivariate analysis revealed that low expression was an independent prognostic factor (hazard ratio, 1.75; 95% confidence interval, 1.08-2.87; P=0.022). The findings of the current study indicate that acts as a putative tumor suppressor that is inactivated through promoter hypermethylation, and serves as a promising biomarker to predict postoperative prognosis in ESCC.