Abstract
Abstract
Gastric cancer (GC), a disease with a very poor prognosis, is the second leading cause of cancer-related deaths worldwide. Although few studies have identified genetic and epigenetic alterations to be involved in gastric carcinogenesis, the molecular pathogenesis of this disease remains incompletely understood, and largely unexplored. With an aim to understand, and identify the molecular pathways important in the pathogenesis of GC, and to identify targets for its detection and therapy, we conducted a pilot microarray-based genome-wide search for identification of epigenetic targets in GC. This study identified 11 prioritized targets of aberrant epigenetic inactivation in gastric neoplasia (GN), including the tight junction protein claudin-11 (CLDN11), the transcription factor BarH-like homeobox (BARX1), basonuclin1 (BNC1), Coagulation factor C homolog (COCH), filamin C gamma (FLNC), cytoglobin B (CYGB), glutamine-fructose-6-phospahe-transaminase-2 (GFPT2), heat-shock-70 kDa protein-6 (HSPA6), snail homolog 1(SNAL1), skin calmodulin-related factor (SCARF), and tumor protein p53 binding protein 2 (TP53BP2). Our initial validations of these targets, particularly, CLDN11, BARX1 and CYGB confirmed these genes to be hypermethylated in their promoter region in gastric cancer cell lines and patient specimens, and their mRNA expression levels to be reduced in gastric cancer tissues and cell lines. More interestingly, our recent preliminary studies demonstrate that overexpression of the BARX1, in GC cells which lack its endogenous expression led to dramatic phenotypic changes in these transfected cells. Moreover, viable cell count was reduced in BARX1 transfected cells. BARX1 is a transcription factor which is known to be involved in the differentiation of embryonic endoderm into stomach. This study for the first time, identifies a potential role of BARX1 in gastric carcinogenesis. Further, large-scale validation studies are underway to confirm the role of BARX1 and other genes as potential targets for GC detection and therapy.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-384. doi:1538-7445.AM2012-LB-384
