Molecule target for treatment and companion diagnostic tool of peritoneal dissemination in gastric cancer

• Project/Area Number: 17H04281
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Nagoya University
• Principal Investigator: KODERA Yasuhiro 名古屋大学, 医学系研究科, 教授 (10345879)
• Co-Investigator(Kenkyū-buntansha): 神田 光郎 名古屋大学, 医学系研究科, 講師 (00644668) ; 林 真路 名古屋大学, 医学部附属病院, 病院講師 (70755503) ; 田中 千恵 名古屋大学, 医学部附属病院, 病院講師 (50589786) ; 小林 大介 名古屋大学, 医学部附属病院, 病院講師 (30635595)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000); Fiscal Year 2019: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2018: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000); Fiscal Year 2017: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
• Keywords: 胃癌 / 腹膜播種 / 分子標的治療

Outline of Final Research Achievements

Peritoneal metastasis is a frequent cause of death in patients with gastric cancer. The pathophysiology and thus targets for treatment are unknown. Synaptotagmin XIII (SYT13) was expressed in patients with peritoneal recurrence of gastric cancer. Inhibition of SYT13 expression in gastric cancer cell lines was associated with decreased invasion and migration ability of the cells. In vivo experiments using a mouse xenograft model of gastric cancer showed that intraperitoneal administration of SYT13-specific small interfering RNA or antibodies significantly inhibited the growth of peritoneal nodules and prolonged survival. SYT13 expression in primary gastric cancer tissues or ascites fluids had diagnostic potential both in the detection and prediction of peritoneal metastasis of gastric cancer. SYT13 may also be a promising target for the treatment of peritoneal metastasis of gastric cancer.

Academic Significance and Societal Importance of the Research Achievements

胃癌において腹膜播種は高頻度な転移再発形式であるにもかかわらず、これを制御しうる分子標的治療薬も精度の高い診断マーカーも発展途上にある。本研究の成果をSYT13阻害薬の創薬と診断キットの開発へとつなげることにより「SYT13発現を評価し、高発現症例に対してはSYT13阻害薬による治療を行う」、というPrecision medicineが実現できる。将来的に、SYT13阻害薬は、胃癌のみならず腹膜播種を高頻度に起こす膵癌、卵巣癌などの他癌種に応用できる可能性も有する。

Research Products

• [Journal Article] The levels of SYT13 and CEA mRNAs in peritoneal lavages predict the peritoneal recurrence of gastric cancer (2019)
  • Author(s): Nakanishi Koki、Kanda Mitsuro、Umeda Shinichi、Tanaka Chie、Kobayashi Daisuke、Hayashi Masamichi、Yamada Suguru、Kodera Yasuhiro
  • Journal Title: Gastric Cancer Volume: 22 Issue: 6 Pages: 1143-1152
  • DOI: 10.1007/s10120-019-00967-3
  • NAID: 40022051066
  • Peer Reviewed
• [Journal Article] Synaptotagmin XIII expression and peritoneal metastasis in gastric cancer. (2018)
  • Author(s): Mitsuro Kanda, Dai Shimizu, Haruyoshi Tanaka, Chie Tanaka, Daisuke Kobayashi, Masamichi Hayashi, Hideki Tanakami, Yukiko Niwa, Suguru Yamada, Tsutomu Fujii, Hiroyuki Sugimoto, Yasuhiro Kodera
  • Journal Title: British Journal of Surgery Volume: 105 Issue: 10 Pages: 1349-1358
  • DOI: 10.1002/bjs.10876
  • Peer Reviewed
• [Presentation] 分子生物学的手法を応用した微小腹腔内遊離胃癌細胞検出法 (2019)
  • Author(s): 中西香企，神田光郎，梅田晋一，田中千恵，小林大介，林 真路，服部憲史，高見秀樹，園原史訓，山田 豪，中山吾郎，小池聖彦，藤原道隆，小寺泰弘
  • Organizer: 第17回日本消化器外科学会大会（JDDW 2019 KOBE）