The Clinical Validity of Urinary Pellet DNA Monitoring for the Diagnosis of Recurrent Bladder Cancer

2024 Fiscal Year Final Research Report

• Project/Area Number: 22K09457
• 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: Iwate Medical University
• Principal Investigator: Tsuyukubo Takashi 岩手医科大学, 医学部, 非常勤医師 (50899359)
• Co-Investigator(Kenkyū-buntansha): 西塚 哲 岩手医科大学, 医歯薬総合研究所, 特任教授 (50453311) ; 小原 航 岩手医科大学, 医学部, 教授 (90337155)
• Project Period (FY): 2022-04-01 – 2025-03-31
• Keywords: 膀胱癌 / バイオマーカー / 尿中DNA / 遺伝子変異 / 再発早期予測 / 治療効果判定 / 無再発の確認 / dPCR

Outline of Final Research Achievements

The aim of this study is to evaluate the clinical validity of using urine pellet DNA (upDNA), monitored by digital PCR (dPCR), as a new biomarker for early recurrence detection in bladder cancer (BC). Patient-specific mutations were monitored by dPCR in upDNA. In 32 patients, dPCR was performed at a mean of 7.2 time points (range: 2-12) for longitudinal monitoring. Clinical recurrence was assessed by imaging and urine cytology and was compared to trends in upDNA variant allele frequency (VAF). A continuously increasing upDNA VAF reaching 1% was defined as molecular recurrence. At least one somatic mutation was traceable in 30 of 32 cases (93.8%). Among 7 cases with clinical recurrence, 5 (71.4%) showed elevated upDNA VAF more than 7 months before clinical diagnosis. upDNA monitoring demonstrated clinical validity in 26 of 30 evaluable cases (86.7%). These findings support upDNA monitoring as a sensitive and practical tool for managing bladder cancer recurrence.

Free Research Field

膀胱癌

Academic Significance and Societal Importance of the Research Achievements

本研究では、膀胱がんの再発を尿に含まれるDNA（upDNA）から高い精度で早期に検出できる方法を開発した。特定の遺伝子変異をデジタルPCRという技術で追跡することで、通常の画像検査よりも数か月早く再発の兆候を捉えられる可能性が示された。これは、一人ひとりの病状に応じた治療判断を支える新たな手段となりうる。再発の早期発見が進めば、治療の効果を高め、患者の負担を減らすとともに、医療資源の効率的な活用にもつながると期待される。