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Analysis of miRNA in urinary and tissue-exudative exosomes of prostate cancer

Research Project

Project/Area Number 19K09688
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56030:Urology-related
Research InstitutionOsaka University

Principal Investigator

Kyosuke Matsuzaki  大阪大学, 医学系研究科, 招へい教員 (90747081)

Co-Investigator(Kenkyū-buntansha) 藤田 和利  近畿大学, 医学部, 准教授 (50636181)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsエクソソーム / 前立腺癌 / miRNA / 尿中バイオマーカー / バイオマーカー / 尿 / 尿中 / 組織
Outline of Research at the Start

PSA高値の前立腺生検陽性患者と生検陰性患者の直腸診後尿中エクソソームに加え、前立腺癌手術検体からEx vivoで生検針を用いて癌組織を採取し、その癌組織を培養することで得られる癌組織由来エクソソームの解析を加えることで、前立腺癌特異的なエクソソーム及びその内包miRNAを同定し、尿中でその検出、定量を行い、PSA高値の患者群内での前立腺癌のバイオマーカーを同定する。さらに微小環境(microenvironment)を制御する前立腺癌細胞特異的エクソソームに含まれるmiRNAを阻害することで癌の浸潤・転移を制御し得る新規治療薬の開発を目指す。

Outline of Final Research Achievements

We isolated EVs from urine obtained following digital rectal examination (DRE) of 14 men with elevated levels of serum prostate-specific antigen (PSA) [negative biopsy (n=4) and PCa (n=10)]. MicroRNAs extracted from EVs were analyzed by microRNA microarray. MicroRNAs miR-30b-3p and miR-126-3p were identified as being overexpressed in urinary EVs of the PCa patients versus the biopsy-negative men. In the independent cohort, these two microRNAs were overexpressed in urinary EVs from the PCa patients versus the negative-biopsy men. Logistic regression analysis adjusted by age and PSA showed that these two microRNAs were significantly associated with the prediction of PCa in biopsy specimens.
Sensitivity and specificity of miR-30b-3p and miR-126-3p for the prediction of PCa were 46.4% and 88.0% and 60.7% and 80.0%, respectively, which were better than those of serum PSA (53.5% and 64.0%,respectively). These miRNAs in urinary EVs could be potential biomarkers of PCa.

Academic Significance and Societal Importance of the Research Achievements

現在前立腺癌診断のバイオマーカーとしてはPSAが挙げられるが偽陽性も多い。確定診断には生検を必要とするが侵襲性の高い検査であり、より低侵襲の検査が望ましい。我々は採取するのに侵襲のない尿に着目し、尿中のバイオマーカーを探索した。エクソソームと呼ばれる人間の体液中に放出される小胞に着目し、前立腺癌患者の尿中エクソソーム内で有意に増加するmiRNAを同定した。これはPSAよりも鋭敏なマーカーであることが示され、非侵襲的な前立腺癌の新規バイオマーカーとしての有用性が期待される。またこのエクソソーム内miRNAを阻害することで癌の増殖などを抑制できる可能性もあり、研究の応用性も高いと考えられる。

Report

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

    (1 results)

All 2020

All Journal Article (1 results)

  • [Journal Article] MiR-30b-3p and miR-126-3p of urinary extracellular vesicles could be new biomarkers for prostate cancer2020

    • Author(s)
      Kyosuke Matsuzaki, Kazutoshi Fujita et al.
    • Journal Title

      Translational Andrology and Urology

      Volume: Publish Ahead of Print Issue: 4 Pages: 1918-1927

    • DOI

      10.21037/tau-20-421

    • Related Report
      2020 Research-status Report

URL: 

Published: 2019-04-18   Modified: 2023-01-30  

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