Development of biomarkers to identify primary cancer sites based on RNA modification information

• Project/Area Number: 20K16414
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Osaka University
• Principal Investigator: Asai Ayumu 大阪大学, 産業科学研究所, 特任助教(常勤) (40783262)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2020: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: RNA修飾 / がん / バイオマーカー / 単分子シーケンサー / トンネルシークエンス技術

Outline of Research at the Start

我々はこれまでに消化器がん患者の末梢血中における特定のmiRNAのメチル化の
検出が高精度ながんの診断に有用であることを報告してきた。RNA修飾は様々ながん種において重要であることが報告されているが、RNA修飾の傾向はがん種毎に異なるため、消化器がん以外ではどんなRNA中のどんな修飾が診断に有用か不明である。そこで、我々が確立したRNA修飾を網羅的に検出可能なトンネルシーケンス技術を用いて、様々ながん種におけるRNA修飾を網羅的に測定することで、がん種特異的なRNA修飾を同定し、末梢血中のRNA修飾情報で高精度にがんの原発巣の特定する診断技術の開発を目指す。

Outline of Final Research Achievements

In this study, in order to apply the cancer diagnostic method by detection of RNA modifications to various cancer types, we worked on establishment of detection technology of RNA modifications by single-molecule sequencing and measurement of RNA modifications in various clinical specimens. As a result, we obtained conductance values of RNA modifications such as N6-methyladenosine (m6A) and 5-methylcytosine (5mC), and established a technique to discriminate them from unmodified nucleic acid. The RNA modifications in a total of 138 samples including gastrointestinal, gynecological, and urological cancers have already been measured, and RNA modifications that could not be detected by existing technologies have been successfully detected. We are currently analyzing cancer-specific RNA modifications and would publish the results.

Academic Significance and Societal Importance of the Research Achievements

従来の計測技術ではRNA修飾を網羅的に計測することは不可能だった。それゆえ、生体内におけるRNA修飾の役割は未だ不明な点が多い。本研究では単分子シーケンサーでRNA修飾技術を確立することで様々なRNA修飾を計測することが可能となり、生命科学研究の発展に大きく貢献するものである。
また、RNA修飾の検出による癌診断は消化器癌の特定のRNA修飾のみでしか検討されていなかった。本研究で様々なRNA修飾を様々な癌種で計測することで、癌種特異的なRNA修飾を同定し、様々な癌種においてRNA修飾の検出による癌診断を可能にすることは癌治療成績の向上に繋がり、臨床上・経済上において波及効果をもたらすものである。

Research Products

• [Journal Article] Direct observation of DNA alterations induced by a DNA disruptor (2022)
  • Author(s): Ohshiro Takahito、Asai Ayumu、Konno Masamitsu、Ohkawa Mayuka、Komoto Yuki、Ofusa Ken、Ishii Hideshi、Taniguchi Masateru
  • Journal Title: Scientific Reports Volume: 12 Issue: 1 Pages: 6945-6945
  • DOI: 10.1038/s41598-022-10725-8
  • Peer Reviewed / Open Access
• [Journal Article] Single-molecule RNA sequencing for simultaneous detection of m6A and 5mC (2021)
  • Author(s): Ohshiro Takahito、Konno Masamitsu、Asai Ayumu、Komoto Yuki、Yamagata Akira、Doki Yuichiro、Eguchi Hidetoshi、Ofusa Ken、Taniguchi Masateru、Ishii Hideshi
  • Journal Title: Scientific Reports Volume: 11 Issue: 1 Pages: 19304-19304
  • DOI: 10.1038/s41598-021-98805-z
  • Peer Reviewed / Open Access
• [Journal Article] Computational healthcare: Present and future perspectives (Review) (2021)
  • Author(s): Asai Ayumu、Konno Masamitsu、Taniguchi Masateru、Vecchione Andrea、Ishii Hideshi
  • Journal Title: Experimental and Therapeutic Medicine Volume: 22 Issue: 6 Pages: 1351-1351
  • DOI: 10.3892/etm.2021.10786
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] COVID-19 Drug Discovery Using Intensive Approaches (2020)
  • Author(s): Asai Ayumu、Konno Masamitsu、Ozaki Miyuki、Otsuka Chihiro、Vecchione Andrea、Arai Takahiro、Kitagawa Toru、Ofusa Ken、Yabumoto Masami、Hirotsu Takaaki、Taniguchi Masateru、Eguchi Hidetoshi、Doki Yuichiro、Ishii Hideshi
  • Journal Title: International Journal of Molecular Sciences Volume: 21 Issue: 8 Pages: 2839-2839
  • DOI: 10.3390/ijms21082839
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Convolutional Neural Network Can Recognize Drug Resistance of Single Cancer Cells (2020)
  • Author(s): Yanagisawa Kiminori、Toratani Masayasu、Asai Ayumu、Konno Masamitsu、Niioka Hirohiko、Mizushima Tsunekazu、Satoh Taroh、Miyake Jun、Ogawa Kazuhiko、Vecchione Andrea、Doki Yuichiro、Eguchi Hidetoshi、Ishii Hideshi
  • Journal Title: International Journal of Molecular Sciences Volume: 21 Issue: 9 Pages: 3166-3166
  • DOI: 10.3390/ijms21093166
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] State-of-the-Art Technology of Model Organisms for Current Human Medicine (2020)
  • Author(s): Konno Masamitsu、Asai Ayumu、Kitagawa Toru、Yabumoto Masami、Ofusa Ken、Arai Takahiro、Hirotsu Takaaki、Doki Yuichiro、Eguchi Hidetoshi、Ishii Hideshi
  • Journal Title: Diagnostics Volume: 10 Issue: 6 Pages: 392-392
  • DOI: 10.3390/diagnostics10060392
  • Peer Reviewed / Open Access
• [Journal Article] Hereditary pancreatitis model by blastocyst complementation in mouse (2020)
  • Author(s): Asai Ayumu、Konno Masamitsu、Kawamoto Koichi、Isotani Ayako、Mori Masaki、Eguchi Hidetoshi、Doki Yuichiro、Arai Takahiro、Ishii Hideshi
  • Journal Title: Oncotarget Volume: 11 Issue: 22 Pages: 2061-2073
  • DOI: 10.18632/oncotarget.27595
  • Peer Reviewed / Open Access
• [Journal Article] Immuno-Surgical Management of Pancreatic Cancer with Analysis of Cancer Exosomes (2020)
  • Author(s): Takeda Yu、Kobayashi Shogo、Kitakaze Masatoshi、Yamada Daisaku、Akita Hirofumi、Asai Ayumu、Konno Masamitsu、Arai Takahiro、Kitagawa Toru、Ofusa Ken、Yabumoto Masami、Hirotsu Takaaki、Vecchione Andrea、Taniguchi Masateru、Doki Yuichiro、Eguchi Hidetoshi、Ishii Hideshi
  • Journal Title: Cells Volume: 9 Issue: 7 Pages: 1645-1645
  • DOI: 10.3390/cells9071645
  • Peer Reviewed / Open Access / Int'l Joint Research