Development of a novel diagnostic biomaker for renal cell carcinoma using bacterial DNA in urinary extracellular vesicles.
| Project/Area Number |
21K20988
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Multi-year Fund |
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| Review Section |
0906:Surgery related to the biological and sensory functions and related fields
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| Research Institution | Osaka University |
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Principal Investigator |
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| Project Period (FY) |
2021-08-30 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 腎細胞癌 / 細胞外小胞 / 細菌DNA / 細菌遺伝情報 / マーカー / 腎癌 / 癌特異的細菌種 / エクソソーム |
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| Outline of Research at the Start |
進行性腎癌の予後は不良であり早期診断が望ましいが、超音波検査をはじめとする画像検査以外の確立されたバイオマーカーは発見されていない。近年、癌局所における臓器特異的な細菌叢の存在や癌患者血液内の細菌叢情報と癌の病期や悪性度との有意な相関が報告されている。われわれは癌特異的エクソソームを用いた16s RNA解析にて、腎癌患者に特異的な尿中細菌叢を見出すことに成功した。当研究では、尿中エクソソームに含まれる細菌遺伝情報についてショットガンシークエンス解析による腎癌特異的細菌”種”の同定を行うことで、非侵襲かつ簡便な腎癌の早期診断を実現する尿診断薬の開発と臨床応用を目標とする。
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| 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.
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| 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。
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Report
(3 results)
Research Products
(1 results)
