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Establishment of monitoring by circulating tumour RNA in patients with metastatic melanoma

Research Project

Project/Area Number 16K10150
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Dermatology
Research InstitutionSapporo Medical University

Principal Investigator

UHARA Hisashi  札幌医科大学, 医学部, 教授 (40201355)

Co-Investigator(Kenkyū-buntansha) 芦田 敦子  信州大学, 学術研究院医学系, 助教 (00596786)
奥山 隆平  信州大学, 学術研究院医学系, 教授 (80292332)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsメラノーマ / リキッドバイオプシー / 血液循環腫瘍RNA / モニタリング / MART-1 / mRNA / Circulating marker / RNA / BRAF / 遺伝子 / MAPK
Outline of Final Research Achievements

Monitoring markers are emerging with which we can frequently and easily evaluate the efficacy of systemic therapy. We established high sensitive quantitative analysis of the mRNA of Tyrosinase, MART-1, gp100 and Tyrosinase related protein in vitro. Because MART-1-mRNA showed the highest sensitivity among the examines molecules, we performed the analysis in the peripheral blood samples of 2 patients with advanced melanoma and 2 normal individuals. The concentration of MART-1-mRNA (Reference gene: GAPDH) was significantly higher in the melanoma patients than normal individuals. However the amount of MART-1 mRNA is not enough to use for monitoring. The result suggested that more suitable candidates as monitoring marker are required, probably in each patient. So, we try now to establish the analytic system to detect individualized candidates for suitable biomarkers by using single-cell RNA sequencing.

Academic Significance and Societal Importance of the Research Achievements

抗がん剤の効果は3ヵ月ごとの画像検査(CTなど)が用いられているが、治療効果をよりリアルタイムにモニターできる検査法が必要である。本研究はメラノーマ細胞に高発現している4つの分子について、患者末梢血中からのRNAの定量的検出を試みた。正常人に比べて患者ではMART-1値が高かった。しかし、現在最も高感度の検出法を用いても末梢血中から検出てきたRNA量は微量であり、モニタリングに使用できる量ではなかった。本研究では現在最も高感度の検出法を確立できた。さらに、末梢血のモニタリングに適した候補分子を患者毎に選別する必要があることを示唆した点より、次の段階の検査法の開発につながったと考える。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (9 results)

All 2018 2017 2016

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 4 results,  Acknowledgement Compliant: 1 results) Presentation (4 results) (of which Invited: 1 results)

  • [Journal Article] Recent advances in therapeutic strategies for unresectable or metastatic melanoma and real-world data in Japan2018

    • Author(s)
      Uhara H
    • Journal Title

      Int J Clin Oncol

      Volume: Electronic Issue: 12 Pages: 1508-1514

    • DOI

      10.1007/s10147-018-1246-y

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Detection of BRAFV600K mutant tumor-derived DNA in the pleural effusion from a patient with metastatic melanoma2017

    • Author(s)
      Sakaizawa K, Ashida A, Uhara H, Okuyama R.
    • Journal Title

      Clin Chem Lab Med

      Volume: 55 Issue: 4 Pages: 92-95

    • DOI

      10.1515/cclm-2016-0634

    • Related Report
      2017 Research-status Report 2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Circulating Tumour DNA for Monitoring Treatment Response to Anti-PD-1 Immunotherapy in Melanoma Patients2017

    • Author(s)
      Ashida A、Sakaizawa K、Uhara H、Okuyama R
    • Journal Title

      Acta Dermato Venereologica

      Volume: 97 Issue: 10 Pages: 1212-1218

    • DOI

      10.2340/00015555-2748

    • NAID

      120007100119

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Quantitative analysis of the BRAF <sup>V600E</sup> mutation in circulating tumor-derived DNA in melanoma patients using competitive allele-specific TaqMan PCR.2016

    • Author(s)
      Ashida A, Sakaizawa K, Mikoshiba A, Uhara H, Okuyama R.
    • Journal Title

      Int J Clin Oncol

      Volume: 21 Issue: 10 Pages: 981-988

    • DOI

      10.1111/1346-8138.13367

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Melanoma with BRAF Mutation in Circulating Cell-free DNA despite no Mutation in the Primary Lesion: A Case Report2016

    • Author(s)
      Atsuko Ashida, Hisashi Uhara, Asuka Mikoshiba, Kaori Sakaizawa, Naomi Kumagai, Hiroshi Koga and Ryuhei Okuyama
    • Journal Title

      Acta Derm Venereol

      Volume: 96 Issue: 1 Pages: 128-129

    • DOI

      10.2340/00015555-2194

    • NAID

      120007100151

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] 皮膚がん治療のこれから2017

    • Author(s)
      宇原 久
    • Organizer
      409回日本皮膚科学会北海道地方会
    • Place of Presentation
      札幌医科大学記念ホール(北海道札幌市)
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] 胸水中のcell-free DNAよりBRAFV600Kを検出できた進行期悪性黒色腫の1例2016

    • Author(s)
      境澤香里、芦田敦子、宇原久、奥山隆平
    • Organizer
      80回日本皮膚科学会東部支部学術大会
    • Place of Presentation
      アクトシティ浜松(静岡県浜松市)
    • Year and Date
      2016-10-29
    • Related Report
      2016 Research-status Report
  • [Presentation] Evaluation of response to nivolumab treatment in patients with metastatic melanoma using circulating tumor DNA2016

    • Author(s)
      芦田敦子、境澤香里、宇原久、奥山隆平
    • Organizer
      75回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-10-06
    • Related Report
      2016 Research-status Report
  • [Presentation] Quantitative analysis of the BRAFV600E in circulating tumor-drived DNA using competitive allele-specific TaqMan PCR in melanoma patients2016

    • Author(s)
      芦田敦子、境澤香里、宇原久、奥山隆平
    • Organizer
      30回表皮細胞研究会
    • Place of Presentation
      アートホテル弘前シティ(青森県弘前市)
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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