Identified genetic signature stimulated peritoneal dissemination in gastric cancer

• Project/Area Number: 15K19899
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Kyushu University (2016); Kumamoto University (2015)
• Principal Investigator: KURASHIGE Junji 九州大学, 医学研究院, 助教 (90594474)
• 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: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 胃癌 / 腹膜播種 / コラーゲン / DDR2 / PLOD2 / extracellular-matrix

Outline of Final Research Achievements

Molecular mechanisms driving peritoneal dissemination still remain poorly understood. Here, we aimed to provide novel insights into the molecular mechanisms that drive the peritoneal dissemination of GC. We performed combined expression analysis with in vivo-selected metastatic cell lines and samples from 200 GC patients to identify driver genes of peritoneal dissemination. We identified a peritoneal dissemination-associated expression signature, whose profile correlated with those of genes related to development, focal adhesion, and the extracellular matrix. Among the genes comprising the expression signature, we identified that genes (DDR2 and PLOD2) as a potential regulator of peritoneal dissemination. These three gene were identified as a driver gene for GC dissemination from the combined expression signature and can potentially serve as a novel therapeutic target for inhibiting GC peritoneal dissemination.

Research Products

• [Journal Article] Integrated molecular profiling of human gastric cancer identifies DDR2 as a potential regulator of peritoneal dissemination (2016)
  • Author(s): Kurashige J, Hasegawa T, Niida A, Sugimachi K, Deng N, Mima K, Uchi R, Sawada G, Takahashi Y, Eguchi H, Inomata M, Kitano S, Fukagawa T, Sasako M, Sasaki H, Sasaki S, Mori M, Yanagihara K, Baba H, Miyano S, Tan P, Mimori K.
  • Journal Title: Sci Rep Volume: 6 Pages: 22371-22371
  • DOI: 10.1038/srep22371
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Integrated multiregional analysis proposing a new model of colorectal cancer evolution (2016)
  • Author(s): R. Uchi (他40名, 山本36番目)
  • Journal Title: PLOS Genetics Volume: 12 Pages: 1005778-1005778
  • DOI: 10.1371/journal.pgen.1005778
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Rapid diagnosis of lymph node metastasis in breast cancer using a new fluorescent method with γ-glutamyl hydroxymethyl rhodamine green. (2016)
  • Author(s): Shinden Y, et al
  • Journal Title: Sci. Rep. Volume: 6 Pages: 27525-27525
  • DOI: 10.1038/srep27525
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Junji Kurashige, Takanori Hasegawa, Atsushi Niida, Kosuke Mima, Ryutaro Uchi, Yuki Takano, Hidetoshi Eguchi, Keishi Sugimachi, Kazuyoshi Yanagihara, Hideo Baba, Koshi Mimori (2016)
  • Author(s): Identified genetic signature stimulated peritoneal dissemination in gastric cancer
  • Organizer: 第75回日本癌学会
  • Place of Presentation: 横浜
  • Year and Date: 2016-10-06
• [Presentation] DDR2-collagen axis promote peritoneal dissemination in gastric cancer. (2016)
  • Author(s): Junji Kurashige, Masaaki Iwatsuki, Daisuke Kuroda, Yuki Kiyozumi, Keisuke Kosumi, Daisuke Izumi, Kzsuto Harada, Ryuma Tokunaga, Hironobu Shigaki, Yoshio Sakamoto, Yuji Miyamoto, Yoshifumi Baba, Naoya Yoshida, Koshi Mimori, Hideo Baba
  • Organizer: 10th AACR-JCA Joint Conference
  • Place of Presentation: Hyatt Regency Maui
  • Year and Date: 2016-02-18
  • Int'l Joint Research
• [Presentation] DDR2-collagen axis promote peritoneal dissemination in gastric cancer. (2015)
  • Author(s): Junji Kurashige, Masaaki Iwatsuki, Daisuke Kuroda, Yuki Kiyozumi, Keisuke Kosumi, Daisuke Izumi, Kzsuto Harada, Ryuma Tokunaga, Hironobu Shigaki, Yoshio Sakamoto, Yuji Miyamoto, Yoshifumi Baba, Naoya Yoshida, Koshi Mimori, Hideo Baba
  • Organizer: 3rd International Conference of Federation of Asian Clinical Oncology
  • Place of Presentation: 国立京都国際会館（京都府）
  • Year and Date: 2015-10-30