1 Department of Molecular Pathology， Hiroshima University Graduate School of Biomedical Sciences

 

2 Department of Gastroenterological and Transplant Surgery， Applied Life Sciences， Institute of Biomedical & Health Sciences， Hiroshima University

 

Genes specifically expressed in cancer cells may be ideal biomarkers and therapeutic targets. In this study， to identify potential molecular markers and therapeutic targets， we searched for gastric cancer-specific genes， and analyzed association with gastric/intestinal mucin phenotype.

 

To identify gastric cancer-specific genes， we used CAST (Escherichia coli ampicillin secretion trap) method using gastric cancer cell lines. Gastric/intestinal mucin phenotype was examined by immunostaining of MUC5AC， MUC6， MUC2， and CD10.

 

By CAST method， we identified several candidate genes including DSC2， TSPAN8， and PCDHB9. DSC2 encodes desmocollin 2， which is one of three known desmocollins. Immunohistochemical analysis demonstrated that 22 (28%) of 80 gastric cancer cases were positive for desmocollin 2. Expression of desmocollin 2 was frequently observed in intestinal phenotype of gastric cancer. TSPAN8 gene encodes transmembrane protein tetraspanin 8. Immunohistochemical analysis of tetraspanin 8 in human gastric cancer tissues revealed that 72 (34%) of 210 cases were positive for tetraspanin 8， and microvessel density was significantly higher in tetraspanin 8-positive gastric cancer than that in tetraspanin 8-negative gastric cancer. Furthermore， univariate and multivariate analyses revealed that tetraspanin 8 expression is an independent prognostic classifier of patients with gastric cancer. Expression of tetraspanin 8 was frequently observed in gastric phenotype of gastric cancer. PCDHB9 gene encodes transmembrane protein protocadherin B9. Immunohistochemical analysis demonstrated that 48 (26%) of 185 gastric cancer cases were positive for protocadherin B9. Protocadherin B9 expression showed a significant correlation with histology and lymphovascular invasion. Expression of protocadherin B9 was not associated with gastric/intestinal phenotype of gastric cancer. PCDHB9 knockdown inhibited peritoneal metastasis in mice model.

 

These molecules may be a novel biomarker and therapeutic target for gastric cancer.