Browse by author
Lookup NU author(s): Professor Bruce Westley,
Dr Felicity May
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
Purpose: Transcriptional profiling showed decreased expression of gastrokine 1 (GKN1) and the related trefoil factor interacting protein (TFIZ1/GKN2) in Helicobacter pylori infection. Decreased GKN1 and GKN2 mRNA expression has been reported in gastric adenocarcinoma. We have examined GKN1 and GKN2 protein expression in a large gastric cancer series, correlated expression with tumor subtype, and evaluated their utility as prognostic biomarkers. Experimental Design: GKN1, GKN2, and the trefoil factors TFF1 and TFF3 were examined in tissue microarrays from 155 distal gastric adenocarcinomas. Immunohistochemical expression was correlated with clinical outcome. GKN1 and GKN2 expression was measured by real-time PCR and Western analysis in samples of gastric cancer and adjacent nonneoplastic mucosa. Results: GKN1 was lost in 78% of diffuse and 42% of intestinal cancers (P < 0.0001, diffuse versus intestinal). GKN2 expression was lost in 85% of diffuse and 54% of intestinal type cancers (P < 0.002). GKN1 and GKN2 down-regulation were confirmed by Western and real-time PCR analysis. Loss of either protein was associated with significantly worse outcome in intestinal-type tumors by univariate analysis; and GKN2 loss remained a predictor of poor outcome in multivariate analysis (P < 0.033).TFF1 was lost in >70%, and TFF3 was expressed in similar to 50% of gastric cancers. Conclusions: Loss of GKN1 and GKN2 expression occurs frequently in gastric adenocarcinomas, especially in the diffuse subtype. GKN1 and GKN2 loss are associated with shorter overall survival in the intestinal subtype.
Author(s): Moss SF, Lee JW, Sabo E, Rubin AK, Rommel J, Westley BR, May FEB, Gao J, Meitner PA, Tavares R, Resnick MB
Publication type: Article
Publication status: Published
Journal: Clinical Cancer Research
Print publication date: 01/07/2008
Acceptance date: 22/04/2008
ISSN (print): 1078-0432
ISSN (electronic): 1557-3265
Publisher: American Association of Cancer Research
Altmetrics provided by Altmetric