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2023 Fiscal Year Final Research Report

Diagnosis of drug sensitivity for castration-resistant prostate cancer using serum exosomes

Research Project

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Project/Area Number 21K09437
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56030:Urology-related
Research InstitutionFujita Health University (2022-2023)
Asahi University (2021)

Principal Investigator

Kato Taku  藤田医科大学, 医学部, 准教授 (50596202)

Co-Investigator(Kenkyū-buntansha) 水谷 晃輔  社会医療法人厚生会中部国際医療センター(研究支援センター), がん研究部, 主任研究員 (80397356)
川上 恭司郎  地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究員 (90589227)
Project Period (FY) 2021-04-01 – 2024-03-31
Keywords去勢抵抗性前立腺癌 / 細胞外小胞 / H19 / RNA-sequencing
Outline of Final Research Achievements

We aimed to evaluate the changes of RNAs in serum extracellular vesicles (EVs/exosomes) from prostate cancer (PC) patients in order to identify novel biomarkers for AR axis-targeted therapy (ARAT)-resistance among castration-resistant PC (CRPC) patients. EVs were isolated from 2 patients before and after acquiring ARAT-resistance. RNA profiling of EVs was performed by RNA-sequencing. The expression levels of selected RNAs in EVs were analyzed by digital droplet PCR (ddPCR) in 85 PC patients. RNA-sequencing and ddPCR revealed that H19 contained in EVs (EV-H19) was significantly increased among ARAT-resistant patients compared to ARAT-naive CRPC or metastatic PC patients. In PC tissue, H19 was negatively correlated with AR protein and AR-activity score and upregulated in neuroendocrine CRPC tissue with low AR expression. EV-H19 may negatively correlate with AR-signaling activity and could be a marker to diagnose ARAT-resistance among CRPC patients.

Free Research Field

がん研究

Academic Significance and Societal Importance of the Research Achievements

前立腺癌の腫瘍マーカーとして前立腺特異抗原(PSA)が普及している。PSAは前立腺癌の治療モニタリングに有用であるが、ARAT投与中の患者ではPSAと病状がしばしば乖離する。本研究ではEV-H19がARAT耐性の新規バイオマーカーとして単独もしくはPSAとの併用により、ARAT耐性をより正確に診断できる可能性を示した。また、EV-H19が前立腺癌の神経内分泌分化を反映している可能性も見出した。以上よりEV-H19は生検を行わず、より低侵襲な方法として前立腺癌のARAT耐性診断及び表現型の変化を捉えられることを示した本研究の意義は大きい。

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Published: 2025-01-30  

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