Identification of a novel molecule relevant to development of peritoneal metastasis from gastric cancer

• Project/Area Number: 15K19879
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Nagoya University
• Principal Investigator: KANDA Mitsuro 名古屋大学, 医学部附属病院, 助教 (00644668)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: Transcriptome解析 / 胃癌 / 腹膜播種 / 個別化治療

Outline of Final Research Achievements

Advanced gastric cancer (GC) frequently recurs because of undetected micrometastases even after curative resection. Peritoneal metastasis has been the most frequent recurrent pattern after gastrectomy and is incurable. We conducted a recurrence pattern-specific transcriptome analysis and synaptotagmin VIII (SYT8) was identified as a candidate biomarker specific to peritoneal metastasis. Expression levels of SYT8 mRNA in GC tissues were elevated in patients with peritoneal recurrence or metastasis. SYT8 levels served as an independent prognostic marker for peritoneal recurrence-free survival of patients with stage II/III GC. Inhibition of SYT8 by GC cells correlated with decreased invasion, migration, and fluorouracil resistance. Intraperitoneal administration of SYT8-siRNA inhibited the growth of peritoneal nodules and prolonged survival of mice engrafted with GC cells. SYT8 represents a promising target for the detection, prediction and treatment of peritoneal metastasis of GC.

Research Products

• [Journal Article] Significance of SYT8 For the Detection, Prediction, and Treatment of Peritoneal Metastasis From Gastric Cancer. (2017)
  • Author(s): Mitsuro Kanda, Dai Shimizu, Haruyoshi Tanaka, Chie Tanaka, Daisuke Kobayashi, Masamichi Hayashi, Naoki Iwata, Yukiko Niwa, Suguru Yamada, Tsutomu Fujii, Hiroyuki Sugimoto, Kenta Murotani, Michitaka Fujiwara, Yasuhiro Kodera
  • Journal Title: Annals of Surgery Volume: 印刷中 Issue: 3 Pages: 495-503
  • DOI: 10.1097/sla.0000000000002096
  • NAID: 120006496425
  • Peer Reviewed
• [Presentation] 新規胃癌腹膜播種関連分子の同定と、その診断的および治療的意義に関する検討 (2017)
  • Author(s): 神田光郎，清水 大，田中晴祥，小林大介，田中千恵，高見秀樹，林 真路，岩田直樹，丹羽由紀子，山田 豪，藤井 努，中山吾郎，杉本博行，小池聖彦，藤原道隆，小寺泰弘
  • Organizer: 第13回日本消化管学会総会学術集会
  • Place of Presentation: 名古屋国際会議場（愛知県・名古屋市熱田区）
  • Year and Date: 2017-02-17
• [Presentation] 胃癌腹膜播種特異的関連分子の発現、機能および5-FU感受性への影響に関する検討 (2017)
  • Author(s): 神田光郎，田中晴祥，田中千恵，小林大介，岩田直樹，山田 豪，中山吾郎，藤井 努，杉本博行，小池聖彦，藤原道隆，小寺泰弘
  • Organizer: 第50回制癌剤適応研究会
  • Place of Presentation: ホテルクレメント徳島（徳島県・徳島市寺島本町）
• [Presentation] Transcriptome解析により同定した胃癌腹膜播種責任分子の機能解析 (2015)
  • Author(s): 神田光郎, 清水 大, 小寺泰弘
  • Organizer: JDDW Tokyo 2015 (第13回日本消化器外科学会大会、第57回日本消化器病学会大会、第19回日本肝臓学会大会、第53回日本消化器がん検診学会大会)
  • Place of Presentation: グランドプリンスホテル新高輪 国際館パミール (東京都港区)
  • Year and Date: 2015-10-08