Gamma-Synuclein serves as a novel prognostic factor of extrahepatic and intrahepatic cholangiocarcinoma via promoting cell migration.

• Project/Area Number: 16K10609
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Keio University
• Principal Investigator: Hibi Taizo 慶應義塾大学, 医学部(信濃町), 共同研究員 (10338072)
• Research Collaborator: OJIMA Hidenori ; TAKEMURA Yusuke ; OSHIMA Go ; KITAGO Minoru ; ABE Yuta ; YAGI Hiroshi ; YAMAGISHI Seri ; HORI Shutaro ; KUBOTA Naoto ; SAKAMOTO Michiie ; KITAGAWA Yuko
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 胆管癌 / Synuclein γ / 胆道癌 / Synucleinγ / 肝内胆管癌 / リンパ節転移 / 消化器外科学 / 肝胆膵外科学 / 浸潤・転移機構

Outline of Final Research Achievements

Methods: One hundred and forty nine cases of extra hepatic cholangiocarcinoma (ECC) and intrahepatic cholangiocarcinoma (ICC) were divided immunohistochemically into SNCG positive and negative groups. Clinicopathological factors and outcomes were compared between the groups. We selected BTC cell lines with SNCG overexpression from 17 BTC cell lines and examined the association between SNCG and cell proliferation or migration.
Results: SNCG expression was observed in 32 (21.4%) cases and correlated with poorer differentiation (P = 0.001) and lymph node metastases (P = 0.001). Multivariate analyses revealed SNCG expression as an independent poor prognostic factor of overall survival (P = 0.008 ) and recurrence-free survival (P = 0.006). In vitro assays demonstrated SNCG silencing suppressed cell migration significantly and a part of cell proliferation.

Academic Significance and Societal Importance of the Research Achievements

道癌は膵癌と同様に予後不良な癌種であり、神経浸潤の頻度も高いがその浸潤、転移機構とSNCGの関連については知られていない。SNCGは新規抗がん剤のターゲットや抗がん剤抵抗性との関連も報告されており、胆道癌におけるSNCGの機能解析により新規抗がん剤開発や治療成績の向上、新規バイオマーカーとなりうると考えられる。

Research Products

• [Journal Article] What is transplant oncology? (2019)
  • Author(s): Hibi T, Sapisochin G
  • Journal Title: Surgery Volume: 165 Issue: 2 Pages: 281-285
  • DOI: 10.1016/j.surg.2018.10.024
  • Peer Reviewed
• [Journal Article] Liver transplantation for hepatobiliary malignancies: a new era of "Transplant Oncology" has begun (2017)
  • Author(s): Hibi T, Itano O, Shinoda M, Kitagawa Y
  • Journal Title: Surg Today Volume: 47 Issue: 4 Pages: 403-15
  • DOI: 10.1007/s00595-016-1337-1
  • Peer Reviewed
• [Presentation] Role of lymph node dissection for intrahepatic cholangiocarcinoma (2017)
  • Author(s): Taizo Hibi
  • Organizer: 2017 Gastrointestinal Cancers Symposium
  • Place of Presentation: San Francisco
  • Year and Date: 2017-01-19
  • Int'l Joint Research
• [Presentation] Liver transplantation for biliary malignancies. Featured symposium. (2017)
  • Author(s): Hibi T, Abe Y, Kitagawa Y.
  • Organizer: The 2017 Joint International Congress of ILTS, ELITA &LICAGE.
  • Int'l Joint Research / Invited
• [Presentation] 肝内胆管癌の局在とリンパ節転移様式に基づいた郭清意義：リンパ節コンパートメント分類の導入 (2017)
  • Author(s): 竹村裕介、日比泰造、北川雄光
  • Organizer: 日本外科学会学術集会
• [Presentation] Patterns of lymph node metastases in intrahepatic cholangiocarcinoma: (2017)
  • Author(s): Yusuke Takemura, Taizo Hibi, Yuko Kitagawa
  • Organizer: Asian pacific hepato-pancreas biliary association canference
  • Int'l Joint Research
• [Presentation] Clinical implication of compartment classification for perihilar Intrahepatic cholangiocarcinoma (2017)
  • Author(s): 竹村裕介、日比泰造、北川雄光
  • Organizer: 日本消化器外科学会総会