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Develophment of promissing markers for diagnosis of lymph node metastasis for uterine cancer and its functional analysis

Research Project

Project/Area Number 18K09299
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56040:Obstetrics and gynecology-related
Research InstitutionJuntendo University

Principal Investigator

terao yasuhisa  順天堂大学, 医学部, 教授 (00348997)

Co-Investigator(Kenkyū-buntansha) 野島 美知夫  順天堂大学, 医学部, 教授 (50198595)
金田 容秀  順天堂大学, 医学部, 准教授 (60445517)
太田 剛志  順天堂大学, 医学部, 非常勤講師 (80407254)
荻島 大貴  順天堂大学, 医学部, 先任准教授 (90327784)
Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords子宮体癌 / リンパ節転移 / バイオマーカー / ロングリードシーケンス / 個別化医療 / 産婦人科 / リスク評価 / リンパ節転移診断マーカー
Outline of Final Research Achievements

Two promissing genes for diagnostic markers for uterine cancer lymph node metastasis were identified by CAGE analysis. One is the TACC2 novel isoform with a new transcription initiation site. Previous studies we have identified multiple transcripts of novel TACC2 with the same novel transcription initiation site. Therefore, as a result of comprehensive nucleotide sequence determination by Oxford Nanopore seqeuncer, more than 800 novel isoforms of TACC2 were identified. This complexity is maintained regardless of cell line, normal endometrium, or endometrial cancer, and there are more splicing variants than previously we thought, and it revieled that downstream function expression may be regulated by transcriptional regulation or a mixture of complex transcripts.

Academic Significance and Societal Importance of the Research Achievements

子宮体癌の再発低リスク症例ではリンパ節郭清は治療的意義に乏しくリンパ節郭清適用の個別化が必要である。申請者は術式適用判断の基準となるリンパ節転移リスク診断マーカーを同定するため、子宮体癌組織RNAをCAGE法により網羅的に解析した。この結果、リンパ節転移診断マーカーとして有用な2遺伝子を同定した。この同定の過程でTACC2新規アイソフォームが複数存在し、最も転移と相関するisoformを同定することは、診断精度の向上に寄与し得る。そこで、新規手法となる全長cDNAの網羅的解析を確立し実施した結果、800種類を超える新規isoformを同定され、転写制御の複雑性を明らかにしえた。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (17 results)

All 2021 2020 2019 2018

All Journal Article (2 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (13 results) (of which Int'l Joint Research: 7 results,  Invited: 2 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Discovery of widespread transcription initiation at microsatellites predictable by sequence-based deep neural network2021

    • Author(s)
      Mathys Grapotte, Manu Saraswat, Chloe Bessiere, and all 474 authors, Laurent Brehelin
    • Journal Title

      Nature Communications

      Volume: 12 Issue: 1 Pages: 3297-3297

    • DOI

      10.1038/s41467-021-23143-7

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Nanopore sequencing reveals TACC2 locus complexity and diversity of isoforms transcribed from an intronic promoter2021

    • Author(s)
      Ito Yosuke、Terao Yasuhisa、Noma Shohei、Tagami Michihira、Yoshida Emiko、Hayashizaki Yoshihide、Itoh Masayoshi、Kawaji Hideya
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1

    • DOI

      10.1038/s41598-021-88018-9

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Presentation] mRNA biomarker identification by using genome-wide gene expression profile, and novel predictive model of combining the biomarkers and clinical variables for diagnosis of lymph node metastases in endometrial cancer.2021

    • Author(s)
      Emiko Yoshida
    • Organizer
      Computational biology and artificial intelligence for personalized medicine, 23rd September 2021
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Novel diagnosis of lymph node metastasis by biomarkers instead of lymphadenectomy for endometrial cancer2021

    • Author(s)
      Emiko Yoshida
    • Organizer
      From Menarche to Menopause" II international in person- online conference, BSMUClinic, St.Shafieva, 2, Ufa, Republic of Bashkortostan
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Validation of ethnic difference in novel predictive biomarker of lymph node metastasis for uterine cancer:International joint research with Russia2020

    • Author(s)
      Emiko Yoshida, Yasuhisa Terao, Yosuke Ito, Yuta Ueno, Masayo Ozawa, Tomoyasu Kato, Hisamori Kato, Kazunari Fujino, Takashi Hirayama, Maiko Yamaguchi, Satoru Takeda, Atsuo Itakura
    • Organizer
      第72回日本産科婦人科学会学術講演会
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Identification of novel companion biomarkers to discriminate the risk of recurrence for endometrial cance2019

    • Author(s)
      Kaidiliayi Sulidan, Yasuhisa Terao, Yosuke Ito, Emiko Yoshida, Shiori Sakayori, Atsuo Itakura
    • Organizer
      第71回日本産科婦人科学会学術講演会
    • Related Report
      2019 Research-status Report
  • [Presentation] Novel initiatives for clinical application: intraoperative-prediction of lymph node metastasis for uterine cancer using isothermal nucleic acid amplification technology2019

    • Author(s)
      Y. Ito, Yasuhisa Terao, Emiko Yoshida, Shiori Sakayori, Atsuo Itakura
    • Organizer
      第71回日本産科婦人科学会学術講演会
    • Related Report
      2019 Research-status Report
  • [Presentation] Novel initiatives for clinical application: Intraoperative-prediction of lymph node metastasis for uterine cancer using isothermal nucleic acid amplification technology2019

    • Author(s)
      Yoshida Emiko, Terao Yasuhisa, Ito Yosuke, Ota Tsuyoshi, Ogishima Daiki, Kaneda Hiroshi, Kusunoki Soshi, Fujino Kazunari, Hirayama Takashi, Kato Hisamori, Takeda Satoru, Itakura Atsuo
    • Organizer
      第71回日本産科婦人科学会学術講演会
    • Related Report
      2019 Research-status Report
  • [Presentation] Novel initiatives for intraoperative assessment of lymph-nodes metastases in endometrial cancer: one-step isothermal nucleic acid amplification based on mRNA expression of primary tumor2019

    • Author(s)
      Yoshida Emiko, Kengo Usui, Yosuke Ito, Yuta Ueno, Masayo Ozawa, Shuko Nojiri, Yasushi Kogo, Tomoyasu Kato, Takashi Ohtsu, Hisamori Kato, Masayoshi Itoh, Hideya Kawaji, Yasuhisa Terao
    • Organizer
      21st European Congress on Gynaecological Oncology
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Development of novel diagnosis method of uterine cancer using lymph node metastasis predictive biomarker for more personalized lymphadenectomy2019

    • Author(s)
      Yoshida Emiko, Kengo Usui, Yosuke Ito, Yuta Ueno, Masayo Ozawa, Shuko Nojiri, Yasushi Kogo, Tomoyasu Kato, Takashi Ohtsu, Hisamori Kato, Masayoshi Itoh, Hideya Kawaji, Yasuhisa Terao
    • Organizer
      The 6th Biennial Meeting of Asian Society of Gynecologic Oncology
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Whole stretch sequencing of various alternative forms from TACC2 gene by MinION sequencer2019

    • Author(s)
      Masyoshi Itoh, Yosuke Ito, Hideya Kawaji, Emiko Yoshida, Shohei Noma, Yoshihide Hayashizaki, Yasuhisa Terao
    • Organizer
      Advances in Genome Biology and Technology (AGBT) 2019
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Searching comprehensive transcript of sex hormone related gene TACC2 using MinION Nanopore sequencer2019

    • Author(s)
      Yosuke Ito, Yasuhisa Terao, Emiko Yoshida, Atsuo Itakura
    • Organizer
      第71回日本産科婦人科学会学術講演会
    • Related Report
      2018 Research-status Report
  • [Presentation] Novel initiatives for clinical application: intraoperative-prediction of lymph node metastasis for uterine cancer using isothermal nucleic acid amplification technology2019

    • Author(s)
      Emiko Yoshida, Yasuhisa Terao, Yosuke Ito, Tsuyoshi Ota, Daiki Ogishima, Hiroshi Kaneda, Soshi Kusunoki, Kazunari Fujino, Takashi Hirayama, Hisamori Kato, Satoru Takeda, Atsuo Itakura
    • Organizer
      第71回日本産科婦人科学会学術講演会
    • Related Report
      2018 Research-status Report
  • [Presentation] 子宮体癌原発巣の遺伝子発現に基づく術中リンパ節転移診断2018

    • Author(s)
      寺尾泰久
    • Organizer
      第60回日本産婦人科腫瘍学会学術講演会
    • Related Report
      2018 Research-status Report
  • [Presentation] Validation of clinical efficacy of lymph node metastasis predictive biomarker and development of rapid diagnosis method for uterine cancer2018

    • Author(s)
      E. Yoshida, Y. Terao, Y. Ito, T. Ota, M. Nojima, D. Ogishima, H. Kaneda, S. Kusunoki, K. Fujino, T. Hirayama, K. Usui, M. Itoh, H. Kawaji, A. Itakura, S. Takeda
    • Organizer
      17th Biennial Meeting of the International Gynecologic Cancer Society (IGCS 2018)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Patent(Industrial Property Rights)] 子宮体がんのリンパ節転移能の評価方法のためのコンパニオンマーカー2021

    • Inventor(s)
      寺尾泰久 吉田惠美子
    • Industrial Property Rights Holder
      寺尾泰久 吉田惠美子
    • Industrial Property Rights Type
      特許
    • Filing Date
      2021
    • Related Report
      2021 Annual Research Report
  • [Patent(Industrial Property Rights)] 子宮体がんのリンパ節転移能の評価方法のためのコンパニオンマーカー2021

    • Inventor(s)
      順天堂、理化学研究所、神奈川県立病院機構
    • Industrial Property Rights Holder
      順天堂、理化学研究所、神奈川県立病院機構
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2021-046188
    • Filing Date
      2021
    • Related Report
      2020 Research-status Report

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Published: 2018-04-23   Modified: 2023-01-30  

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