Establishment of "Liquid Staging" using urine samples

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08045
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Veterinary medical science
• Research Institution: The University of Tokyo
• Principal Investigator: Nakagawa Takayuki 東京大学, 大学院農学生命科学研究科(農学部), 准教授 (40447363)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: Liquid-biopsy / BRAF / vimentin / EMT / TCC / digital PCR

Outline of Final Research Achievements

The purpose of this study was to establish "Liquid Biopsy" that can diagnose and confirm the progress of transitional cell carcinoma of the dog, whose early definitive diagnosis is very difficult, from urine samples. For diagnosis, we established a Digital PCR method that can detect BRAF gene mutations, which are frequently found in canine transitional cell carcinoma, with high sensitivity, and succeeded in its clinical application. We investigated the development of the tumor by targeting epithelial-mesenchymal transition, and clarified that the mesenchymal marker vimentin is significantly associated with survival in canine transitional cell carcinoma. Based on these results, it was considered that the basic data of Liquid biopsy for tumor diagnosis and pathological condition grasping was formed by urine samples.

Free Research Field

臨床獣医学

Academic Significance and Societal Importance of the Research Achievements

これまでの検査では犬移行上皮癌の早期診断は非常に困難であり、積極的な治療であっても生存期間は1年未満であった。本研究成果によって早期診断が実現したことで、犬移行上皮癌症例の生存予後は大きく改善することが期待されるだけでなく、尿サンプルを用いた"Liquid Biospy"の成功例の先駆けとなったと考える。また犬移行上皮癌においてvimentinが有意な予後指標となることを初めて見出したが、これも臨床応用可能な予後マーカーとなるだけでなく、浸潤性の高い犬移行上皮癌の分子生物学的な性状の解析やより効果的な治療法開発に向けた基盤的データとして意義ある成果と考えられた。