Development of Diagnostics and Therapeutics targeting GNG4 and ASGR2.

• Project/Area Number: 17K16538
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Nagoya University
• Principal Investigator: TANAKA Haruyoshi 名古屋大学, 医学部附属病院, 病院助教 (80793504)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 胃癌 / 肝転移 / 網羅的解析 / ASGR2 / GNG4

Outline of Final Research Achievements

Gastric cancer is still one of the diseases with poor prognosis. Among them, strategy for stage IV gastric cancer with distant metastasis, especially liver metastasis, is currently under development. We focused on this gastric cancer liver metastasis and developed a specialized diagnostic treatment. We collected cancer tissues from gastric cancer patients with liver metastasis and found GNG4 and ASGR2 as genes that specifically function (express) in liver metastasis patients. Cells that suppressed the function of this gene (knockout/knockdown; KO/KD) had reduced proliferation. The ability forming liver metastases in mice was reduced in KO/KD cells. GNG4 and ASGR2 might to have the potential for diagnostics and/or therapeutics specifically for liver metastasis.

Academic Significance and Societal Importance of the Research Achievements

この研究成果により、転移先臓器に特異的な遺伝子発現の変動が起こるという仮説が胃癌肝転移においても成り立つことが証明された。また、胃癌肝転移に関連する遺伝子が２つ発見され、これらの分子生物学的な理解が深まったといえる。今後この2つの遺伝子を標的とした胃癌肝転移に対する新規抗癌剤や診断薬の開発につながる可能性がある。

Research Products

• [Journal Article] Pattern-Specific Transcriptomics Identifies ASGR2 as a Predictor of Hematogenous Recurrence of Gastric Cancer (2018)
  • Author(s): Haruyoshi Tanaka, Mitsuro Kanda, Takashi Miwa, Chie Tanaka, Daisuke Kobayashi, Shinichi Umeda, Masahiro Shibata, Masaya Suenaga, Norifumi Hattori, Masamichi Hayashi, Naoki Iwata, Suguru Yamada, Goro Nakayama, Michitaka Fujiwara, Yasuhiro Kodera
  • Journal Title: Molecular Cancer Research Volume: 16 Issue: 9 Pages: 1420-1429
  • DOI: 10.1158/1541-7786.mcr-17-0467
  • Peer Reviewed
• [Presentation] Pattern-specific Transcriptomics Identifies ASGR2 as a Predictor of Hematogenous Recurrence of Gastric Cancer (2018)
  • Author(s): Haruyoshi Tanaka, Mitsuro Kanda, Masaya Suenaga, Masamichi Hayashi, Chie Tanaka, Suguru Yamada, Goro Nakayama, Masahiko Koike, Michitaka Fujiwara, Yasuhiro Kodera
  • Organizer: 第77回日本癌学会学術総会