Abstract
Abstract
Gastric cancer (GC) remains the second most-common cause of cancer deaths globally, with an overall 5-year survival rate below 20%. The poor prognosis of this cancer, due largely to delayed diagnosis, would be greatly improved by the identification of biomarkers to stratify risk and accelerate diagnosis. In search of such markers, a pilot microarray-based genome-wide search conducted by our group identified claudin-11 (CLDN11), a tight junction (TJ) protein, as a potential target of epigenetic inactivation in gastric cancers. Claudin-11 belongs to the family of claudin proteins, which contains more than 23 members. In recent years, it has been demonstrated by us and others that members of the claudin gene family are involved in various human cancers. Our data identified the CLDN11 promoter region as being heavily hypermethylated in GC tissues and cell lines. Moreover, CLDN11 mRNA was found to be expressed only in primary noncancerous gastric mucosal tissues, as well as in an immortalized normal gastric epithelial cell line, whereas it was silenced in all GC tissues and cell lines examined. Interestingly, siRNA-mediated downregulation of CLDN11 in CLDN11-expressing gastric cells was also associated with cancer-related phenotypic changes, specifically increased cell motility and invasiveness. Our recent data also demonstrates that CLDN11 methylation levels can differentiate GC from its corresponding non-cancerous normal gastric mucosae with 100% sensitivity and specificity. A deeper understanding of the timing of CLDN11 inactivation during the development and progression of gastric neoplasia will lead to the development of potential early detection and prognostic biomarkers. Further, large-scale prospective validation studies of this alteration as a predictive biomarker for GC development are warranted.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-89.
