Development of liquid biopsy for rapid molecular pathological diagnosis of highly malignant tumors and its application to precision medicine

• Project/Area Number: 19H03559
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 52010:General internal medicine-related
• Research Institution: Shiga University of Medical Science
• Principal Investigator: DAIGO Yataro 滋賀医科大学, 医学部, 教授 (30345029)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000); Fiscal Year 2021: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2020: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2019: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
• Keywords: 分子病態診断 / バイオマーカー

Outline of Research at the Start

本研究では極めて悪性度の高い胸部難治癌（肺癌、食道癌、胸膜中皮腫）の組織・血液試料と多数の遺伝子・蛋白質の解析技術や血液中の微量分子の検出技術を基盤として、実用的な臨床診断に応用可能な癌由来分子（バイオマーカー）を同定・検証することをめざす。これらに基づき、バイオマーカーによる発癌リスクや未病・早期癌を検出する血液診断法、さらには体質や癌の個性に対応した個別化医療（プレシジョン医療）に応用可能な診断法の開発を進め、将来的な癌年齢層の健康寿命の延長とQOLの向上に役立つ情報を得る。

Outline of Final Research Achievements

In this study, we screened cancer specific molecules (biomarkers) that can be applicable to practical cancer diagnosis through comprehensive and highly sensitive gene and protein analysis of clinical biomaterials from the patients with highly malignant thoracic cancer. Among them, we identified candidate diagnostic biomarkers for cancer risk diagnosis, early cancer detection, and personalized medicine (precision medicine). We reported the results of this study at various conferences and published some manuscripts in international academic journals. In this study, we obtained fundamental information towards the development of new personalized medicine for cancers.

Academic Significance and Societal Importance of the Research Achievements

難治癌はその予防と超早期での発見、診断後は治療後の再発予防に向けた精密なフォローアップが重要であり、新たな高精度の診断法の開発が求められている。癌の病態を反映した生体試料を用いて最新の分子分析技術で遺伝子や蛋白質の解析を行い、実用化を念頭に置いた研究デザインで新しい診断方法の基盤情報を取得することで癌の予防に向けたリスク診断や早期診断に加え、癌の悪性度に基づいた治療選択とフォローによる個別化医療の開発に繋がり、癌の予後改善による健康寿命の延長やQOLの向上が期待される。

Research Products

• [Journal Article] Investigation of miRNA expression profiles using cohort samples reveals potential early detectability of colorectal cancers by serum miR-26a-5p before clinical diagnosis (2022)
  • Author(s): Hishida Asahi、Yamada Hiroya、Ando Yoshitaka、Okugawa Yoshinaga、Shiozawa Manabu、Miyagi Yohei、Daigo Yataro、Toiyama Yuji、Shirai Yumiko、Tanaka Koji、Kubo Yoko、Okada Rieko、Nagayoshi Mako、Tamura Takashi、Mori Atsuyoshi、Kondo Takaaki、Hamajima Nobuyuki、Takeuchi Kenji、Wakai Kenji
  • Journal Title: Oncology Letters Volume: 23 Issue: 3 Pages: 87-87
  • DOI: 10.3892/ol.2022.13207
  • Peer Reviewed / Open Access / Int'l Joint Research
• [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] Phosphorylation of hTERT at threonine 249 is a novel tumor biomarker of aggressive cancer with poor prognosis in multiple organs (2022)
  • Author(s): Matsuda Y, Yamashita T, Ye J, Yasukawa M, Yamakawa K, Mukai Y, Machitani M, Daigo Y, Miyagi Y, Yokose T, Oshima T, Ito H, Morinaga S, Kishida T, Minamoto T, Yamada S, Takei J, Kaneko MK, Kojima M, Kaneko S, Masaki T, Hirata M, Haba R, Kontani K, Kanaji N, Miyatake N, Okano K, Kato Y, Masutomi K
  • Journal Title: J Pathol Volume: 257 Issue: 2 Pages: 172-185
  • DOI: 10.1002/path.5876
  • Peer Reviewed / Open Access
• [Journal Article] Biphasic prognostic significance of PD-L1 expression status in patients with early- and locally advanced-stage non-small cell lung cancer (2021)
  • Author(s): Teramoto K, Igarashi T, Kataoka Y, Ishida M, Hanaoka J, Sumimoto H, Daigo Y
  • Journal Title: Cancer Immunol Immunother Volume: 70 Issue: 4 Pages: 1063-1074
  • DOI: 10.1007/s00262-020-02755-w
  • Peer Reviewed
• [Journal Article] Large-scale genome-wide association study in a Japanese population identifies novel susceptibility loci across different diseases (2020)
  • Author(s): Ishigaki K, Akiyama M, Kanai M, Takahashi A, Kawakami E, Sugishita H, Sakaue S, Matoba N, Low SK, Okada Y, Yamaji T, et al
  • Journal Title: Nature Genetics Volume: 52 Issue: 7 Pages: 669-679
  • DOI: 10.1038/s41588-020-0640-3
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Tuberculosis infection and lung adenocarcinoma: Mendelian randomization and pathway analysis of genome-wide association study data from never-smoking Asian women (2020)
  • Author(s): Wong JYY, Zhang H, Hsiung CA, Goto A, et al.
  • Journal Title: Genomics Volume: 112 Issue: 2 Pages: 1223-1232
  • DOI: 10.1016/j.ygeno.2019.07.008
  • 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] 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] Clinical significance of PD-L1-positive cancer-associated fibroblasts in pN0M0 non-small cell lung cancer (2019)
  • Author(s): Koji Teramoto, Tomoyuki Igarashi, Yoko Kataoka, Mitsuaki Ishida, Jun Hanaoka, Hidetoshi Sumimoto, Yataro Daigo
  • Journal Title: Lung Cancer Volume: 137 Pages: 56-63
  • DOI: 10.1016/j.lungcan.2019.09.013
  • 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] 生体試料による支援活動 (2022)
  • Author(s): 醍醐 弥太郎
  • Organizer: CoBiA令和3年度若手支援研究成果発表会
• [Presentation] 生体試料による支援活動 (2020)
  • Author(s): 醍醐 弥太郎
  • Organizer: CoBiA令和2年度若手支援研究成果発表会
• [Presentation] がんゲノム医療 (2020)
  • Author(s): 醍醐弥太郎
  • Organizer: 第3回薬理ゲノミクスセミナー
  • Invited
• [Presentation] がんの分子病態に基づいたトランスレーショナルリサーチ (2019)
  • Author(s): 醍醐弥太郎
  • Organizer: 第17回日本臨床腫瘍学会
  • Invited
• [Book] 遺伝子医学 (2020)
  • Author(s): 牛島俊和、醍醐弥太郎 他
  • Total Pages: 168
  • Publisher: メディカル ドゥ
  • ISBN: 9784909508058