Details

Autor(en) / Beteiligte

• Wilhelm, Franziska
• Böger, Christine
• Krüger, Sandra
• Behrens, Hans-Michael
• Röcken, Christoph

Titel

Troy is expressed in human stomach mucosa and a novel putative prognostic marker of intestinal type gastric cancer

Ist Teil von

• Oncotarget, 2017-08, Vol.8 (31), p.50557-50569

Ort / Verlag

United States: Impact Journals LLC

Erscheinungsjahr

2017

Quelle

EZB-FREE-00999 freely available EZB journals

Beschreibungen/Notizen

• Epithelial stem cells of gastrointestinal tissues are characterized and controlled by an active Wnt signaling. Recently, the Wnt target gene has been proposed as a neoplastic marker in the murine intestine. In this study, we explored the putative tumor biological significance of Troy in humans by using immunohistochemistry (104 cases), quantitative RT-PCR (50 cases) and cell culture experiments (MKN45, MKN74). In the non-neoplastic gastric mucosa, Troy was expressed by Muc5AC-positive foveolar epithelium, parietal cells, chief cells and cells of the intestinal metaplasia. In gastric cancer, Troy was found in the desmoplastic stroma and tumor cells. The overall staining intensity of the tumor cells was lower compared with the adjacent non-neoplastic mucosa, Troy was found significantly more commonly in intestinal compared with diffuse type gastric cancer (p=0.001) and correlated inversely with tumor grade (p<0.001) and nodal spread (p=0.025). In the intestinal type, loss of Troy-expression was associated with a significantly worse overall survival (p=0.006). Subsequent cell culture experiments showed a Wnt dependent expression of Troy and a reduced colony formation ability of Troy-overexpressing MKN45-cells. Our results lead to the conjecture that Troy is also a negative regulator of WNT signaling in gastric cancer, which affects patient outcome.