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Identification of novel methylation markers in HPV-associated oropharyngeal cancer for precision medicine

Research Project

Project/Area Number 17K16904
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Otorhinolaryngology
Research InstitutionHamamatsu University School of Medicine

Principal Investigator

Imai Atsushi  浜松医科大学, 医学部附属病院, 助教 (30794309)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
KeywordsHPV関連癌 / リキッドバイオプシー / 中咽頭癌 / メチル化 / cell free DNA / 循環腫瘍DNA / 頭頸部癌 / 個別化医療 / 腫瘍循環細胞 / メチル化解析
Outline of Final Research Achievements

Genome-wide discovery using RNA sequencing and reduced representation bisulfite sequencing yielded 21 candidates for methylation-targeted genes. A verification study using Q-MSP identified 10 genes that showed an increase recurrence in methylation groups with oropharyngeal cancer (OPC). Further study on ctDNA in HPV-associated OPC showed that three genes (CALML5, DNAJC5G, and LY6D) had a high predictive ability as emerging biomarkers for a validation set, each capable of discriminating between the plasma of the patients from healthy individuals. Among pre-treatment ctDNA samples, methylated CALML5, DNAJC5G, and LY6D were observed in 8/8 (100%), 7/8 (87.5%), and 7/8 (87.5%) samples, respectively. Methylated CALML5, DNAJC5G, and LY6D were found in 2/8 (25.0%), 0/8 (0%), and 1/8 (12.5%) of the final samples in the series, respectively. Here, we present the relationship between the methylation status of three genes and cancer recurrence for risk classification of HPV-associated OPC cases.

Academic Significance and Societal Importance of the Research Achievements

今回の研究は、リキッドバイオプシーによるHPV関連中咽頭癌の腫瘍状態を見極められるマーカーを探索することが目的であった。3種類の遺伝子のDNAメチル化を調べることによって治療後の腫瘍の状態、再発による腫瘍の増大を検知できる手法を開発することができた。従来、CT、MRI、PET-CTによる画像評価が治療に行われていたが、患者への負担が少ない採血から得られたctDNAによって、腫瘍の状態を評価することができ今後の臨床に応用されていくことが期待される。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (13 results)

All 2019 2018 2017

All Journal Article (10 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 10 results,  Open Access: 9 results) Presentation (2 results) (of which Int'l Joint Research: 1 results) Book (1 results)

  • [Journal Article] SALL2 Is a Novel Prognostic Methylation Marker in Patients with Oral Squamous Carcinomas: Associations with SALL1 and SALL3 Methylation Status.2019

    • Author(s)
      Imai A, Mochizuki D, Misawa Y, Nakagawa T, Endo S, Mima M, Yamada S, Kawasaki H, Kanazawa T, Misawa K.
    • Journal Title

      DNA and Cell Biology

      Volume: 38 Issue: 7 Pages: 678-687

    • DOI

      10.1089/dna.2018.4597

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 5-Hydroxymethylcytosine and ten-eleven translocation dioxygenases in head and neck carcinoma2019

    • Author(s)
      Misawa K, Yamada S, Mima M, Nakagawa T, Kurokawa T, Imai A, Mochizuki D, Morita K, Ishikawa R, Endo S and Misawa Y
    • Journal Title

      Journal of Cancer

      Volume: 10(21) Issue: 21 Pages: 5306-5314

    • DOI

      10.7150/jca.34806

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Epigenetic modification of SALL1 as a novel biomarker for the prognosis of early stage head and neck cancer2018

    • Author(s)
      Misawa Kiyoshi、Misawa Yuki、Imai Atsushi、Mochizuki Daiki、Endo Shiori、Mima Masato、Ishikawa Ryuji、Kawasaki Hideya、Yamatodani Takashi、Kanazawa Takeharu
    • Journal Title

      Journal of Cancer

      Volume: 9 Issue: 6 Pages: 941-949

    • DOI

      10.7150/jca.23527

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Analysis of Site-Specific Methylation of Tumor-Related Genes in Head and Neck Cancer: Potential Utility as Biomarkers for Prognosis2018

    • Author(s)
      Misawa Kiyoshi、Mochizuki Daiki、Imai Atsushi、Mima Masato、Misawa Yuki、Mineta Hiroyuki
    • Journal Title

      Cancers

      Volume: 10 Issue: 1 Pages: 27-27

    • DOI

      10.3390/cancers10010027

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The neuropeptide genes SST, TAC1, HCRT, NPY, and GAL are powerful epigenetic biomarkers in head and neck cancer: A site-specific analysis2018

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

      Clinical Epigenetics

      Volume: 10 Issue: 1 Pages: 52-52

    • DOI

      10.1186/s13148-018-0485-0

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] New Approach to Prevention of Postoperative Delirium in Patients Undergoing Head and Neck Cancer Surgery2018

    • Author(s)
      Kamijo Tomoyuki、Matsumoto Komei、Onitsuka Tetsuro、Imai Atsushi、Iida Yoshiyuki、Nagaoka Masato、Kitani Takashi
    • Journal Title

      Nippon Jibiinkoka Gakkai Kaiho

      Volume: 121 Issue: 1 Pages: 31-37

    • DOI

      10.3950/jibiinkoka.121.31

    • NAID

      130006338115

    • ISSN
      0030-6622, 1883-0854
    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Risk and prognostic factors for multiple primary carcinomas in patients with head and neck cancer2017

    • Author(s)
      Hosokawa S, Takahashi G, Okamura J, Imai A, Mochizuki D, Takizawa Y Yamatodani T, Misawa K, Mineta H
    • Journal Title

      Jpn J Clin Oncol

      Volume: 48(2) Issue: 2 Pages: 124-129

    • DOI

      10.1093/jjco/hyx178

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genes encoding neuropeptide receptors are epigenetic markers in patients with head and neck cancer: a site-specific analysis2017

    • Author(s)
      Misawa K, Imai A, Mochizuki D, Misawa Y, Endo S, Hosokawa S, Ishikawa R, Mima M, Shinmura K, Kanazawa T, Mineta H
    • Journal Title

      Oncotarget

      Volume: 8(44) Issue: 44 Pages: 76318-76328

    • DOI

      10.18632/oncotarget.19356

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Epigenetic silencing of SALL3 is an independent predictor of poor survival in head and neck cancer2017

    • Author(s)
      Misawa K, Mochizuki D, Imai A, Misawa Y, Endo S, Mima M, Kawasaki H, Carey TE, Kanazawa T
    • Journal Title

      Clin Epigenetics

      Volume: 9 Issue: 1 Pages: 64-64

    • DOI

      10.1186/s13148-017-0363-1

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Evaluation of epigenetic inactivation of vascular endothelial growth factor receptors in head and neck squamous cell carcinoma.2017

    • Author(s)
      Misawa Y, Misawa K, Kawasaki H, Imai A, Mochizuki D, Ishikawa R, Endo S, Mima M, Kanazawa T, Iwashita T, Mineta H.
    • Journal Title

      Tumour Biol.

      Volume: 39 Issue: 7 Pages: 1-15

    • DOI

      10.1177/1010428317711657

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Prognostic value of aberrant promoter hypermethylation of tumor-related genes in early-stage head and neck cancer2018

    • Author(s)
      Atsushi Imai, Kiyoshi Misawa, Daiki Mochizuki, Takeharu Kanazawa, Hiroyuki Mineta
    • Organizer
      109rd AACR Annual Meeting 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 同時性4臓器6重複癌の1例.2017

    • Author(s)
      今井篤志、望月大極、岡村 純、三澤 清、細川誠二、峯田周幸
    • Organizer
      第41回頭頸部癌学会
    • Related Report
      2017 Research-status Report
  • [Book] ENTONI No.210(2017年9月・増大号) 術後せん妄に対する向精神病薬の使い方. もう迷わない耳鼻咽喉科疾患に対する向神病薬の使い方2017

    • Author(s)
      今井篤志、峯田周幸
    • Total Pages
      6
    • Publisher
      全日本病院出版会
    • ISBN
      9784865195040
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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