Development of a novel diagnostic biomaker for renal cell carcinoma using bacterial DNA in urinary extracellular vesicles.

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K20988
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0906:Surgery related to the biological and sensory functions and related fields
• Research Institution: Osaka University
• Principal Investigator: Uemura Toshihiro 大阪大学, 医学部附属病院, 医員 (60905941)
• Project Period (FY): 2021-08-30 – 2023-03-31
• Keywords: 腎細胞癌 / 細胞外小胞 / 細菌DNA

Outline of Final Research Achievements

Eighty-eight patients with renal cell carcinoma and 10 healthy donors were enrolled as a discovery cohort, and extracellular vesicles were collected from various samples and 16S rRNA metagenomic analysis was performed. Because urine samples were affected by bacteriuria even in healthy donors and we were unable to identify bacterial DNA that would be useful for diagnosis, we focused on blood, which has a smaller biomass, and identified three types of bacterial DNA that were abundant in serum extracellular vesicles of patients with RCC. These were combined to create an index for the diagnosis of RCC, which had an AUC of 0.88, sensitivity of 89%, and specificity of 40%. In a similar analysis in a validation cohort of 32 renal cancer patients and 16 healthy donors, the created diagnostic index had a high sensitivity of 90%, suggesting its usefulness as a screening test.

Free Research Field

泌尿器科

Academic Significance and Societal Importance of the Research Achievements

臨床応用された腎癌の診断マーカーはなく、画像検査以外の早期診断は困難である。診断時には転移を有することも少なくなく、簡便かつ高感度なスクリーニング検査の開発が求められている。循環細胞外小胞に含まれる細菌DNAを用いた診断指標は、早期腎癌（病理学的T分類 StageⅠ）においても有用であり、腫瘍量に依存しないバイオマーカーとして期待される。