Synaptotagmin XIII expression and peritoneal metastasis in gastric cancer

Author:

Kanda M1ORCID,Shimizu D1,Tanaka H1,Tanaka C1,Kobayashi D1,Hayashi M1,Takami H1,Niwa Y1,Yamada S1ORCID,Fujii T1,Sugimoto H1,Kodera Y1

Affiliation:

1. Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan

Abstract

Abstract Background Peritoneal metastasis is a frequent cause of death in patients with gastric cancer. The aim of this study was to identify molecules responsible for mediating peritoneal metastasis of gastric cancer. Methods Transcriptome and bioinformatics analyses were conducted to identify molecules associated with peritoneal metastasis. The therapeutic effects of intraperitoneally administered small interfering (si) RNA were evaluated using mouse xenograft models. Expression of mRNA and protein was determined in gastric tissues from patients with gastric cancer. Results Synaptotagmin XIII (SYT13) was expressed at significantly higher levels in patients with peritoneal recurrence, but not in those with hepatic or distant lymph node recurrence. Inhibition of SYT13 expression in a gastric cancer cell line transfected with SYT13-specific siRNA (siSYT13) was associated with decreased invasion and migration ability of the cells, but not with proliferation and apoptosis. Intraperitoneal administration of siSYT13 significantly inhibited the growth of peritoneal nodules and prolonged survival in mice. In an analysis of 200 patients with gastric cancer, SYT13 expression in primary gastric cancer tissues was significantly greater in patients with peritoneal recurrence or metastasis. A high level of SYT13 expression in primary gastric cancer tissues was an independent risk factor for peritoneal recurrence. Conclusion SYT13 expression in gastric cancer is associated with perioneal metatases and is a potential target for treatment.

Funder

Japanese Foundation for Multidisciplinary Treatment of Cancer

Grant-in-Aid for Encouragement of Young Scientists

Grant-in-Aid for Scientific Research

Centre for Advanced Medicine and Clinical Research at Nagoya University

Novartis Pharma Research

Yasuda Medical Foundation

Aichi Health Promotion Foundation

Publisher

Oxford University Press (OUP)

Subject

Surgery

Reference28 articles.

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