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

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K09688
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Osaka 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
• Keywords: エクソソーム / 前立腺癌 / miRNA / 尿中バイオマーカー

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.

Free Research Field

泌尿器癌

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。