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Epigenetic real-time monitoring of head and neck cancer

Research Project

Project/Area Number 20K09689
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56050:Otorhinolaryngology-related
Research InstitutionHamamatsu University School of Medicine

Principal Investigator

Misawa Kiyoshi  浜松医科大学, 医学部, 教授 (90334979)

Co-Investigator(Kenkyū-buntansha) 今井 篤志  浜松医科大学, 医学部附属病院, 講師 (30794309)
望月 大極  浜松医科大学, 医学部附属病院, 助教 (40467246)
山口 裕貴  浜松医科大学, 医学部附属病院, 診療助教 (60837821)
石川 竜司  浜松医科大学, 医学部, 助教 (90436931)
Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2021: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2020: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Keywordsエピゲノム動態 / リキッドバイオプシー / リアルタイムモニター法 / 頭頸部癌 / 原発不明癌 / クロマチン動態
Outline of Research at the Start

①5hmCのゲノム上の分布情報をTAB-Seq法によって調べる。②クロマチン動態に焦点をあてたエピゲノム状態を調べる。③リキッドバイオプシーによるリアルタイムモニタリング法を確立する。この3つの研究により、Epigenetic inactivationとactivationの両面からのアプローチによる頭頸部癌におけるエピゲノム機構の解明とリアルタイムモニター法の確立を目指す。頭頸部癌の新規治療法の確立、早期癌の発見につながるモニター法の開発を目指す。

Outline of Final Research Achievements

The goal of this study has been to elucidate the epigenetic mechanisms in head and neck cancer by using both epigenetic inactivation and activation approaches and to establish a real-time monitoring method. As an outcome, we were able to find methylation markers by liquid biopsy in oral cancer by methyl analysis of opioid receptors.In addition, blood samples were routinely drawn and collected to evaluate epigenomic dynamics in HPV-associated mesopharyngeal carcinoma. In addition, we have conducted a study to identify the primary site by liquid biopsy in cancers of unknown primary site.

Academic Significance and Societal Importance of the Research Achievements

再発・転移を有する進行頭頸部癌において、従来の抗癌剤・分子標的薬に加えて免疫チェックポイント阻害薬が加わったことで薬剤シーケンスの選択の幅が広がった。そのため、腫瘍再発などの病勢や化学療法の効果・予後予測を判定するバイオマーカーが求められている。今回、エピジェネティックな変化を計測することで病態・治療効果予測に関わるHPV関連・非関連頭頸部癌のバイオマーカーを確立を目指した。リキッドバイオプシーによるctDNA解析で、口腔癌、HPV関連中咽頭癌さらに原発不明癌症例の解析を行った。CT、MRI、PET-CTによる画像評価と違った精度での治療効果判定、再発病変の検出ができる可能性を示した。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (26 results)

All 2023 2022 2021 2020

All Journal Article (15 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 15 results,  Open Access: 13 results) Presentation (11 results) (of which Invited: 4 results)

  • [Journal Article] Tumorigenic activation around <scp>HPV</scp> integrated sites in head and neck squamous cell carcinoma2023

    • Author(s)
      Mima Masato、Okabe Atsushi、Hoshii Takayuki、Nakagawa Takuya、Kurokawa Tomoya、Kondo Satoru、Mizokami Harue、Fukuyo Masaki、Fujiki Ryoji、Rahmutulla Bahityar、Yoshizaki Tomokazu、Hanazawa Toyoyuki、Misawa Kiyoshi、Kaneda Atsushi
    • Journal Title

      International Journal of Cancer

      Volume: 152 Issue: 9 Pages: 1847-1862

    • DOI

      10.1002/ijc.34439

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Association between human papillomavirus particle production and the severity of recurrent respiratory papillomatosis2023

    • Author(s)
      Yamada Satoshi、Itoh Toshiya、Ikegami Taro、Imai Atsushi、Mochizuki Daiki、Nakanishi Hiroshi、Ishikawa Ryuji、Kita Junya、Nakamura Yuki、Takizawa Yoshinori、Okamura Jun、Noda Yoshihiro、Iwashita Toshihide、Hariyama Takahiko、Suzuki Mikio、Misawa Kiyoshi、Kawasaki Hideya
    • Journal Title

      Scientific Reports

      Volume: 13 Issue: 1 Pages: 5514-5514

    • DOI

      10.1038/s41598-023-32486-8

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Impact of radiation dose on treatment of radiotherapy and superselective intra-arterial cisplatin in maxillary cancer.2023

    • Author(s)
      Konishi K, Kamiya M, Ohira K, Hirata M, Wakabayashi K, Ikenohira T, Kosugi T, Ushio T, Imai A, Mochizuki D, Yamaguchi Y, Tanahashi Y, Misawa K, Goshima S, Nakamura K.
    • Journal Title

      Anticancer Research

      Volume: 43 Issue: 6 Pages: 2859-2864

    • DOI

      10.21873/anticanres.16455

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identifying Active Progeny Virus Particles in Formalin-Fixed, Paraffin-Embedded Sections Using Correlative Light and Scanning Electron Microscopy2023

    • Author(s)
      Itoh Toshiya、Yamada Satoshi、Ohta Isao、Meguro Shiori、Kosugi Isao、Iwashita Toshihide、Itoh Hiroaki、Kanayama Naohiro、Okudela Koji、Sugimura Haruhiko、Misawa Kiyoshi、Hariyama Takahiko、Kawasaki Hideya
    • Journal Title

      Laboratory Investigation

      Volume: 103 Issue: 1 Pages: 100020-100020

    • DOI

      10.1016/j.labinv.2022.100020

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Repression of DERL3 via DNA methylation by Epstein-Barr virus latent membrane protein 1 in nasopharyngeal carcinoma2022

    • Author(s)
      Kondo S, Okabe A, Nakagawa T, Matsusaka K, Fukuyo M, Rahmutulla B, Dochi H, Mizokami H, Kitagawa Y, Kurokawa T, Mima M, Endo K, Sugimoto H, Wakisaka N, Misawa K, Yoshizaki T, Kaneda A.
    • Journal Title

      Biochimica et Biophysica Acta - Molecular Basis of Disease

      Volume: 1869(2) Issue: 2 Pages: 166598-166598

    • DOI

      10.1016/j.bbadis.2022.166598

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] エピゲノム異常と頭頸部がん2022

    • Author(s)
      三澤 清
    • Journal Title

      耳鼻咽喉科臨床

      Volume: 115 Pages: 357-366

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] 頭頸部癌とリキッドバイオプシー2022

    • Author(s)
      三澤 清
    • Journal Title

      耳鼻咽喉科展望

      Volume: 65 Pages: 132-137

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Novel prognostic value and potential utility of opioid receptor gene methylation in liquid biopsy for oral cavity cancer2022

    • Author(s)
      Ishikawa Ryuji、Imai Atsushi、Mima Masato、Yamada Satoshi、Takeuchi Kazutaka、Mochizuki Daiki、Shinmura Daichi、Kita Jun-ya、Nakagawa Takuya、Kurokawa Tomoya、Misawa Yuki、Nakanishi Hiroshi、Takizawa Yoshinori、Misawa Kiyoshi
    • Journal Title

      Current Problems in Cancer

      Volume: 46 Issue: 2 Pages: 100834-100834

    • DOI

      10.1016/j.currproblcancer.2021.100834

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prolonged activation of cytomegalovirus early gene e1-promoter exclusively in neurons during infection of the developing cerebrum2021

    • Author(s)
      Kosugi Isao、Arai Yoshifumi、Baba Satoshi、Kawasaki Hideya、Iwashita Toshihide、Tsutsui Yoshihiro
    • Journal Title

      Acta Neuropathologica Communications

      Volume: 9 Issue: 8 Pages: 2165-2172

    • DOI

      10.7150/jca.54760

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prostanoid receptor genes confer poor prognosis in head and neck squamous cell carcinoma via epigenetic inactivation.2020

    • Author(s)
      Misawa K, Mima M, Yamada S, Imai A, Mochizuki D, Ishikawa R, Kita J, Yamaguchi Y, Endo S, Misawa Y and Mineta H
    • Journal Title

      Journal of Translational Medicine

      Volume: 18(1) Issue: 1 Pages: 31-31

    • DOI

      10.1186/s12967-020-02214-1

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Neuropeptide receptor genes GHSR and NMUR1 are candidate epigenetic biomarkers and predictors for surgically treated patients with oropharyngeal cancer.2020

    • Author(s)
      Misawa K, Mima M, Yamada S, Misawa Y, Imai A, Mochizuki D, Nakagawa T, Kurokawa T, Oguro M, Ishikawa R, Yamaguchi Y, Endo S, Kawasaki H, Kanazawa Takeharu and Mineta H
    • Journal Title

      Scientific Reports

      Volume: 10(1) Issue: 1 Pages: 1007-1007

    • DOI

      10.1038/s41598-020-57920-z

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] G protein-coupled receptor genes, PTGDR1, PTGDR2, and PTGIR, are candidate epigenetic biomarkers and predictors for treated patients with HPV-associated oropharyngeal cancer.2020

    • Author(s)
      Misawa K, Imai A, Kanazawa T, Mima M, Yamada S, Misawa Y, Mochizuki D, Yamada T, Shinmura D, Ishikawa R, Kita J, Yamaguchi Y, Misawa Y and Mineta H
    • Journal Title

      Microorganisms

      Volume: 8(10) Issue: 10 Pages: 1504-1504

    • DOI

      10.3390/microorganisms8101504

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Overexpression of Sal-like protein 4 in head and neck cancer: epigenetic effects and clinical correlations2020

    • Author(s)
      Misawa Kiyoshi、Misawa Yuki、Mima Masato、Yamada Satoshi、Imai Atsushi、Mochizuki Daiki、Nakagawa Takuya、Kurokawa Tomoya、Endo Shiori、Kawasaki Hideya、Brenner John Chadwick.、Mineta Hiroyuki
    • Journal Title

      Cellular Oncology

      Volume: 43 Issue: 4 Pages: 631-641

    • DOI

      10.1007/s13402-020-00509-5

    • NAID

      120007026256

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Identification of novel methylation markers in HPV-associated oropharyngeal cancer: genome-wide discovery, tissue verification and validation testing in ctDNA.2020

    • Author(s)
      Misawa K, Imai A, Matsui H, Kanai A, Misawa Y, Mochizuki D, Mima M, Yamada S, Kurokawa T, Nakagawa T and Mineta H
    • Journal Title

      Oncogene

      Volume: 39(24) Issue: 24 Pages: 4741-4755

    • DOI

      10.1038/s41388-020-1327-z

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Long interspersed nuclear element 1 hypomethylation has novel prognostic value and potential utility in liquid biopsy for oral cavity cancer.2020

    • Author(s)
      Misawa K, Yamada S, Mima M, Nakagawa T, Kurokawa T, Imai A, Mochizuki D, Shinmura D, Yamada T, Kita J, Ishikawa R, Yamaguchi Y, Misawa Y, Kanazawa T, Kawasaki H and Mineta H
    • Journal Title

      Biomarker Research

      Volume: 8 Issue: 1 Pages: 53-53

    • DOI

      10.1186/s40364-020-00235-y

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] HARRP Scoreによる再発性呼吸器乳頭腫症の再発予測2023

    • Author(s)
      三澤 清、山田智史
    • Organizer
      第3回日本耳鼻咽喉科免疫アレルギー感染症学会
    • Related Report
      2023 Annual Research Report
  • [Presentation] シンポジウム HPV関連中咽頭癌のリキッドバイオプシーメチル化解析とその応用2023

    • Author(s)
      三澤 清
    • Organizer
      第47回日本頭頸部癌学会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 原発不明がんにおける原発探索のためのメチル化解析について2023

    • Author(s)
      三澤 清
    • Organizer
      第36回日本口腔咽頭科学会
    • Related Report
      2023 Annual Research Report
  • [Presentation] リキッドバイオプシーによるメチル化解析について2022

    • Author(s)
      三澤 清
    • Organizer
      第35回日本口腔・咽頭科学会
    • Related Report
      2022 Research-status Report
  • [Presentation] 原発不明癌におけるリキッドバイオプシーについて2022

    • Author(s)
      三澤 清
    • Organizer
      第73回日本気管食道科学会
    • Related Report
      2022 Research-status Report
  • [Presentation] ヒト乳頭腫ウイルスによる発癌メカニズムと遺伝子修飾による転写調節異常について2021

    • Author(s)
      三澤清、美馬勝人、山田智史、黒川友哉、中川拓也
    • Organizer
      第1回日本耳鼻咽喉科免疫アレルギー感染症学会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] Identification of novel methylation markers predictors for treated patients with HPV-associated oropharyngeal cancer: genome-wide discovery, tissue verification and validation testing in cfDNA2021

    • Author(s)
      三澤 清
    • Organizer
      第59回日本癌治療学会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 頭頸部癌の個別化医療を目指したエピゲノム解析2020

    • Author(s)
      三澤清、今井篤志、望月大極、山田智史、瀧澤義徳、細川誠二、峯田周幸
    • Organizer
      第30回日本頭頸部外科学会
    • Related Report
      2020 Research-status Report
  • [Presentation] Identification of novel methylation markers in HPV-associated oropharyngeal cancer.2020

    • Author(s)
      三澤清、美馬勝人、峯田周幸
    • Organizer
      第79回日本癌学会
    • Related Report
      2020 Research-status Report
  • [Presentation] シンポジウム 頭頸部癌のエピゲノム解析と臨床応用2020

    • Author(s)
      三澤 清
    • Organizer
      第44回日本頭頸部癌学会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] 頭頸部がんにおける脱メチル化とテロメア長について2020

    • Author(s)
      三澤清、今井篤志、望月大極、三澤由幾、遠藤志織、美馬勝人、山田智史、瀧澤義徳、細川誠二、峯田周幸
    • Organizer
      第121回日本耳鼻咽喉科学会総会
    • Related Report
      2020 Research-status Report

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Published: 2020-04-28   Modified: 2025-01-30  

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