CAST法を用いた新規スキルス胃癌特異的膜蛋白質の同定 : TM9SF3は癌の浸潤に関与し、 予後因子となる

Objective: Scirrhous type gastric cancer is highly aggressive and has a worse prognosis because of its rapid cancer cell infiltration, accompanied by extensive stromal fibrosis. The aim of this study is to identify genes that encode transmembrane proteins frequently expressed in scirrhous type gastric cancer. Methods: We generated Escherichia coli ampicillin secretion trap (CAST) libraries from 2 human scirrhous type gastric cancer tissues and compared with a normal stomach CAST library. By sequencing 2,880 colonies from scirrhous CAST libraries, we identified a list of candidate genes. Results: We focused on TM9SF3 gene because it has the highest clone count and immunohistochemical analysis demonstrated that 46 (50%) of 91 gastric cancer cases were positive for TM9SF3 and it was observed frequently in scirrhous type gastric cancer. TM9SF3 expression showed a significant correlation with the depth of invasion, tumor stage and undifferentiated type of gastric cancer. There was a strong correlation between TM9SF3 expression and poor survival prognosis of patients, validated in two separate cohorts, by immunostaining or qRT‐PCR. Transient knockdown of the TM9SF3 gene by siRNA showed decreased tumor cell invasive capacity. Conclusion: Our results indicate that TM9SF3 might be a potential diagnostic and therapeutic target for scirrhous type gastric cancer.広島大学(Hiroshima University)博士(医学)Philosophy in Medical Sciencedoctora