Identification of biomarker and therapeutic target for lung cancer

• Project/Area Number: 19K07884
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52010:General internal medicine-related
• Research Institution: The University of Tokyo
• Principal Investigator: Takano Atsushi 東京大学, 医科学研究所, 特任講師 (50582607)
• Co-Investigator(Kenkyū-buntansha): 醍醐 弥太郎 東京大学, 医科学研究所, 特任教授 (30345029)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 腫瘍学 / 分子標的治療 / 腫瘍マーカー / 新規治療分子 / バイオマーカー / 肺がん

Outline of Research at the Start

われわれは、これまで肺がんの遺伝子発現情報をもとに、肺がんで高発現し、正常で発現のほとんどないタンパクを標的にして、肺がんの腫瘍マーカー、治療標的分子として報告してきた。最近では、次世代シークエンサー、digital PCRなど、これまで検出できなかったわずかな変化を検出することが可能となっているため、容易に行え、少ない負担で採取可能な血液検体を用いて、近年開発された検出器を用いて、高感度に肺がんの早期診断や予後予測を行うマーカーを同定し、更にはがんの前段階での診断や予防を目標としている。またがん特異的マーカーを新規治療標的分子とした開発も並行して行う。

Outline of Final Research Achievements

We detected target nucleotides in exosome by digital PCR and autoantibody against target protein by ELISA.
We select candidate genes that were aberrantly expressed in cancers, but barely expressed in various normal organs. We confirmed the expression of targets in cancer cells and tissues by real-time quantitative PCR, Western blotting, and immunocytochemical staining analyses. Immunohistochemical analysis confirmed the differences in survival times among cancer patient with or without candidate protein. We confirmed that target protein is essential for cell growth or motility of cancer cells by inhibiting candidate protein expression using siRNAs. Morphological changes of siRNAs-transfected cells by live-cell imaging using time-lapse microscopy were detected. Small compounds against target protein inhibit the growth of cancer cells.

Academic Significance and Societal Importance of the Research Achievements

エキソソーム中などに含まれる核酸や血中自己抗体を用いて、がんを早期に検出することは、治癒可能な早期に肺がんを発見可能とし、予後改善につながってくる。一方、がんに特異的な発現をし、正常組織での発現が少なければ、有望ながんの治療標的分子候補となり得る。このような治療標的分子を阻害剤で抑制しても、正常組織への影響は少なく、特異的にがんの増殖を抑制することが可能であり、有望な治療法となりうる。がんの治療は、初回、２回目の治療までは一定の効果はあるが、再発も多く、正常組織への影響の少ない治療薬を長く使用できるようにすることはがん患者の予後改善に有用であると考えられる。

Research Products

• [Journal Article] Characterization of Opa interacting protein 5 as a new biomarker and therapeutic target for oral cancer (2022)
  • Author(s): Ming Zhu Atsushi Takano Bayarbat Tsevegjav Yoshihiro Yoshitake Masanori Shinohara Yataro Daigo
  • Journal Title: International journal of oncology Volume: 60(3) Issue: 3 Pages: 27-27
  • DOI: 10.3892/ijo.2022.5317
  • Peer Reviewed / Open Access
• [Journal Article] Holliday junction recognition protein as a prognostic biomarker and therapeutic target for oral cancer (2022)
  • Author(s): Bayarbat Tsevegjav, Atsushi Takano, Ming Zhu, Yoshihiro Yoshitake, Masanori Shinohara, Yataro Daigo
  • Journal Title: International journal of oncology Volume: 60(3) Issue: 3 Pages: 27-27
  • DOI: 10.3892/ijo.2022.5316
  • Peer Reviewed / Open Access
• [Journal Article] Characterization of KIF20A as a prognostic biomarker and therapeutic target for different subtypes of breast cancer. (2020)
  • Author(s): Nakamura M, Takano A, Thang PM, Tsevegjav B, Zhu M, Yokose T, Yamashita T, Miyagi Y, Daigo Y.
  • Journal Title: Int J Oncol. Volume: 57 Issue: 1 Pages: 277-288
  • DOI: 10.3892/ijo.2020.5060
  • Peer Reviewed / Open Access
• [Journal Article] Detection of neoantigen-reactive T cell clones based on the clonal expansion using next-generation sequencing of T cell receptor β complementarity complementarity-determining region 3 (2019)
  • Author(s): Hidetoshi Sumimoto, Atsushi Takano, Koji Teramoto, Yataro Daigo
  • Journal Title: Journal of Immunological Methods Volume: 476 Pages: 1-14
  • DOI: 10.1016/j.jim.2019.112679
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Interleukin-34 expression in ovarian cancer: A possible correlation with disease progression. (2019)
  • Author(s): Hiraku Endo, Naoki Hama, Muhammad Baghdad, Kozo Ishikawa, Ryo Otsuka Haruka Wada, Hiroshi Asano, Daisuke Endo, Yosuke Konno, Tatsuya Kato, Hidemichi Watari, Akiko Tozawa, Nao Suzuki, Tomoyuki Yokose, Atsushi Takano, Hisamori Kato, Yohei Miyagi, Yataro Daigo, Ken-ichiro Seino.
  • Journal Title: International Immunology Volume: 32 Issue: 3 Pages: 175-186
  • DOI: 10.1093/intimm/dxz074
  • NAID: 120006980030
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Prognostic value of IL-34 in colorectal cancer patients. (2019)
  • Author(s): Kobayashi T, Baghdadi M, Han N, Murata T, Hama N, Otsuka R, Wada H, Shiozawa M, Yokose T, Miyagi Y, Takano A, Daigo Y, Seino KI.
  • Journal Title: Immunol Med. Volume: 42(4) Issue: 4 Pages: 169-175
  • DOI: 10.1080/25785826.2019.1691429
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Stromal fibroblasts induce metastatic tumor cell clusters via epithelial-mesenchymal plasticity. (2019)
  • Author(s): Matsumura Y, Ito Y, Mezawa Y, Sulidan K, Daigo Y, Hiraga T, Mogushi K, Wali N, Suzuki H, Itoh T, Miyagi Y, Yokose T, Shimizu S, Takano A, Terao Y, Saeki H, Ozawa M, Abe M, Takeda S, Okumura K, Habu S, Hino O, Takeda K, Hamada M, Orimo A.
  • Journal Title: Life Sci Alliance Volume: 2(4):e201900425. Issue: 4 Pages: 1-24
  • DOI: 10.26508/lsa.201900425
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] CD26 expression is attenuated by TGF-β and SDF-1 autocrine signaling on stromal myofibroblasts in human breast cancers (2019)
  • Author(s): Mezawa Y, Daigo Y, Takano A, Miyagi Y, Yokose T, Yamashita T, Morimoto T, Hino O, Orimo A.
  • Journal Title: Cancer Med Volume: 8 Issue: 8 Pages: 3936-3948
  • DOI: 10.1002/cam4.2249
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] CD271 is a negative prognostic factor and essential for cell proliferation in lung squamous cell carcinoma (2019)
  • Author(s): Mochizuki Mai、Nakamura Mao、Sibuya Rie、Okazaki Toshimasa、Abe Jiro、Nakagawa Takayuki、Takahashi Satomi、Yamazaki Tomoko、Imai Takayuki、Takano Atsushi、Ito Hiroyuki、Yokose Tomoyuki、Miyagi Yohei、Daigo Yataro、Sato Ikuro、Satoh Kennichi、Sugamura Kazuo、Yamaguchi Kazunori、Tamai Keiichi
  • Journal Title: Laboratory Investigation Volume: - Issue: 9 Pages: 1349-1362
  • DOI: 10.1038/s41374-019-0246-5
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Characterization of OASEP1 as a potential prognostic biomarker and therapeutic target for oral cancer (2022)
  • Author(s): Atsushi Takano, Yoshihiro Yoshitake, Masanori Shinohara, Yataro Daigo,
  • Organizer: 第19回日本臨床腫瘍学会学術集会
• [Presentation] Characterization of URST1 as a new prognostic biomarker and therapeutic target for oral cancer (2021)
  • Author(s): Atsushi Takano, Yoshihiro Yoshitake, Masanori Shinohara, Yataro Daigo,
  • Organizer: 第65回 日本人類遺伝学会
• [Presentation] Characterization of URST1 and its downstream pathways involved in malignant potential of lung cancer (2021)
  • Author(s): Atsushi Takano, Yohei Miyagi, Yataro Daigo,
  • Organizer: 第80回日本癌学会学術総会
• [Presentation] Identification of URST1 as a cancer biomarker and therapeutic target for lung cancer (2021)
  • Author(s): Atsushi Takano, Yohei Miyagi, Yataro Daigo
  • Organizer: AACR 2021 annual meeting
  • Int'l Joint Research
• [Presentation] Characterization of URST1 as a biomarker and therapeutic target for oral cancer (2021)
  • Author(s): Atsushi Takano, Yoshihiro Yoshitake, Masanori Shinohara, Yataro Daigo
  • Organizer: 第18回日本臨床腫瘍学会学術総会
• [Presentation] Characterization of URST1 as a cancer biomarker and therapeutic target for lung cancer (2020)
  • Author(s): Atsushi Takano, Yohei Miyagi, Yataro Daigo
  • Organizer: AACR meeting 2021
  • Int'l Joint Research
• [Presentation] 大学病院でのがん薬物療法レジメン運用における診療の質向上とリスク管理に関する後方視研究 (2020)
  • Author(s): 高野 淳、寺本 晃治、住本 秀敏、醍醐 弥太郎
  • Organizer: 第117回 日本内科学会総会
• [Presentation] Identification of OASEP1 as a biomarker and therapeutic target for oral cancer (2020)
  • Author(s): Atsushi Takano, Yoshihiro Yoshitake, Masanori Shinohara, Yataro Daigo
  • Organizer: 第65回 日本人類遺伝学会学術総会
• [Presentation] Characterization of URST1 as a biomarker and therapeutic target for lung cancer (2020)
  • Author(s): Atsushi Takano, Yohei Miyagi, Yataro Daigo
  • Organizer: 第79回日本癌学会学術総会
• [Presentation] 大学病院での診療の質向上にむけたがん薬物療法レジメン管理の後方視研究 (2019)
  • Author(s): 高野 淳, 住本 秀敏, 寺本 晃治, 醍醐 弥太郎
  • Organizer: 第116回日本内科学会
• [Presentation] New target OASEP1 as a biomarker and therapeutic target for oral cancer (2019)
  • Author(s): Atsushi Takano, Yoshihiro Yoshitake, Masanori Shinohara, Yataro Daigo
  • Organizer: The Japanese Cancer Association 78th Meeting
• [Presentation] Characterization of cytokinesis-related protein, URST1 as a cancer biomarker and therapeutic target for oral cancer. (2019)
  • Author(s): Atsushi Takano, Yoshihiro Yoshitake, Masanori Shinohara, Yataro Daigo
  • Organizer: The 64th Annual Meeting of Japanese Society of Human Genetics
• [Presentation] Identification of OASEP1 as a biomarker and therapeutic target for oral cancer (2019)
  • Author(s): Atsushi Takano, Yoshihiro Yoshitake,Masanori Shinohara, Yataro Daigo,
  • Organizer: 2019 臨床腫瘍学会
• [Presentation] Characterization of URST1 as a biomarker and therapeutic target for precision medicine of lung cancer (2019)
  • Author(s): Atsushi Takano, Yohei Miyagi, Yataro Daigo
  • Organizer: 2019AACR meeting
  • Int'l Joint Research
• [Book] 入門臨床腫瘍内科学 (2020)
  • Author(s): 日本臨床腫瘍学会
  • Total Pages: 335
  • Publisher: 南江堂
  • ISBN: 9784524225422