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 approximately 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.
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 approximately 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.
Authors: Takasuke Yamachika; J Lawrence Werther; Carol Bodian; Mark Babyatsky; Masae Tatematsu; Yoshitaka Yamamura; Anli Chen; Steven Itzkowitz Journal: Clin Cancer Res Date: 2002-05 Impact factor: 12.531
Authors: K Shiozaki; S Nakamori; M Tsujie; J Okami; H Yamamoto; H Nagano; K Dono; K Umeshita; M Sakon; H Furukawa; M Hiratsuka; T Kasugai; S Ishiguro; M Monden Journal: Int J Oncol Date: 2001-10 Impact factor: 5.650
Authors: Terence E Martin; C Thomas Powell; Zunde Wang; Somnath Bhattacharyya; Margaret M Walsh-Reitz; Kan Agarwal; F Gary Toback Journal: Am J Physiol Gastrointest Liver Physiol Date: 2003-08 Impact factor: 4.052
Authors: Olga Kim; Jung Hwan Yoon; Won Suk Choi; Hassan Ashktorab; Duane T Smoot; Suk Woo Nam; Jung Young Lee; Won Sang Park Journal: Gastric Cancer Date: 2017-02-01 Impact factor: 7.370
Authors: Yon Hui Kim; Han Liang; Xiuping Liu; Ju-Seog Lee; Jae Yong Cho; Jae-Ho Cheong; Hoguen Kim; Min Li; Thomas J Downey; Matthew D Dyer; Yongming Sun; Jingtao Sun; Ellen M Beasley; Hyun Cheol Chung; Sung Hoon Noh; John N Weinstein; Chang-Gong Liu; Garth Powis Journal: Cancer Res Date: 2012-03-20 Impact factor: 12.701
Authors: Jessica H Geahlen; Carlo Lapid; Kaisa Thorell; Igor Nikolskiy; Won Jae Huh; Edward L Oates; Jochen K M Lennerz; Xiaolin Tian; Victoria G Weis; Shradha S Khurana; Samuel B Lundin; Alan R Templeton; Jason C Mills Journal: Physiol Genomics Date: 2013-05-28 Impact factor: 3.107
Authors: Trevelyan R Menheniott; Louise O'Connor; Yok Teng Chionh; Jan Däbritz; Michelle Scurr; Benjamin N Rollo; Garrett Z Ng; Shelley Jacobs; Angelique Catubig; Bayzar Kurklu; Stephen Mercer; Toshinari Minamoto; David E Ong; Richard L Ferrero; James G Fox; Timothy C Wang; Philip Sutton; Louise M Judd; Andrew S Giraud Journal: J Clin Invest Date: 2016-03-14 Impact factor: 14.808