Establishment of a new tumor marker of colorectal cancer that is a combination of high expression genes and low expression genes

• Project/Area Number: 16K19195
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Laboratory medicine
• Research Institution: Yamaguchi University
• Principal Investigator: NISHIOKA Mitsuaki 山口大学, 医学部附属病院, 臨床検査技師 (70738963)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: TROY / LGR5 / 大腸癌 / デジタルPCR / Wnt経路

Outline of Final Research Achievements

Wnt signaling plays an important role in development and progression of colorectal cancer (CRC). We found that TROY gene involved in the Wnt/β-catenin signaling pathway can be a prognostic biomarker in CRC patients. Especially, in patients with stage II and III CRC, TROY overexpression was the independent prognostic factor of disease-free survival after operation. These results suggest that analysis of TROY might help predict clinical outcome in patients with CRC. Since TROY is relatively low expression in colon, we found that the measurement of digital PCR is more sensitive than that of real time quantitative PCR on the prognosis in CRC patients when we measured TROY mRNA expression level.

Academic Significance and Societal Importance of the Research Achievements

大腸癌の進行度を示すステージ分類(I～IV)において、ステージI～IIIのほぼ全てで外科的切除が第一選択となる。手術後の再発率はステージI、II、IIIでそれぞれ4.1%、13.1%、30.8%と、ステージが上がると再発率も上昇している。そのため大腸癌の手術後は必要に応じて化学療法を行うが、その明確な適応基準がなく曖昧である。また、切除不能な転移再発を起こした場合、予後に大きく寄与すると考えられるため、再発を予測の評価方法の開発が課題である。本研究によりII、III大腸癌の術後の再発予測においてTROY遺伝子が大きく関与していること発見した。この成果は今後の大腸癌手術後の再発予防に貢献できる。

Research Products

• [Journal Article] TROY is a promising prognostic biomarker in patients with colorectal cancer (2018)
  • Author(s): Nishioka Mitsuaki、Suehiro Yutaka、Sakai Kouhei、Matsumoto Toshihiko、Okayama Naoko、Mizuno Hidekazu、Ueno Koji、Suzuki Nobuaki、Hashimoto Shinichi、Takami Taro、Hazama Shoichi、Nagano Hiroaki、Sakaida Isao、Yamasaki Takahiro
  • Journal Title: Oncology Letters Volume: 15 Pages: 5989-5994
  • DOI: 10.3892/ol.2018.8079
  • Peer Reviewed / Open Access
• [Journal Article] Fusobacterium nucleatum as a prognostic marker of colorectal cancer in a Japanese population (2017)
  • Author(s): Yamaoka Yuko、Suehiro Yutaka、Hashimoto Shinichi、Hoshida Tomomi、Fujimoto Michiyo、Watanabe Michiya、Imanaga Daiki、Sakai Kouhei、Matsumoto Toshihiko、Nishioka Mitsuaki、Takami Taro、Suzuki Nobuaki、Hazama Shoichi、Nagano Hiroaki、Sakaida Isao、Yamasaki Takahiro
  • Journal Title: Journal of Gastroenterology Volume: 53 Issue: 4 Pages: 517-524
  • DOI: 10.1007/s00535-017-1382-6
  • Peer Reviewed
• [Journal Article] Highly sensitive stool DNA testing of Fusobacterium nucleatum as a marker for detection of colorectal tumours in a Japanese population. (2016)
  • Author(s): Suehiro Y, Sakai K, Nishioka M, Hashimoto S, Takami T, Higaki S, Shindo Y, Hazama S, Oka M, Nagano H, Sakaida I, Yamasaki T.
  • Journal Title: Ann Clin Biochem Volume: April 28 Issue: 1 Pages: 86-91
  • DOI: 10.1177/0004563216643970
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] 大腸癌患者における droplet digital PCR を用いた TROY発現解析の有用性について (2019)
  • Author(s): 西岡光昭
  • Organizer: 第65回 日本臨床検査医学会学術集会
• [Remarks] 山口大学医学部附属病院 検査部
  • URL: http://ds.cc.yamaguchi-u.ac.jp/~jnaka/kensabu/index.html