| Project/Area Number |
17K16788
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Urology
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| Research Institution | Osaka University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | エクソソーム / 膀胱癌 / 尿 / バイオマーカー / proteomics / 尿中バイオマーカー / プロテオミクス / たんぱく / 尿路上皮癌 / タンパク |
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| Outline of Final Research Achievements |
Extracellular vesicles(EVs) were isolated from urine from 7 bladder cancer(BC) patients and 4 healthy controls(HC) by ultracentrifugation.We also extracted EVs directly from surgically resected viable BC tissues(tissue exudative EV;Te-EVs).EVs protein were labeled with TMT and analyzed by LC-MS/MS.We identified 1960 proteins in urinary EVs and 1538 proteins in Te-EV, among which CLD4 was detected in urine of only BC patients and was also enriched in Te-EV. CLD4 in urinary EVs was verified in 70 independent urine samples(BC[n=40],HV[n=30]) using SRM/MRM.CLD4 in urinary EVs was significantly higher in BC group than in HC group (fold-change=9.82, p-value )and was significantly associated with pT stage (p-value for trend <0.0001). The AUC was 0.845, and the sensitivity and specificity of the model at the best cutoff value were 72.5% and 86.7%, respectively.The diagnostic performance of CLD4 was better than that of urine cytology ((Youden's index 0.592 vs 0.475).
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| Academic Significance and Societal Importance of the Research Achievements |
今回の研究では、膀胱癌患者の尿中エクソソームに加え、癌組織から分泌される癌特異的エクソソームを同時に解析することで、より癌特異度の高いエクソソームを同定することができ、結果としてより有用なバイオマーカーを探索、同定することができた。このCLD4は膀胱癌のスクリーニングとして用いるだけでなく、癌組織から分泌されていることより、エクソソームを介して微小環境(microenvironment)を制御している可能性もあり、これを阻害することで新規治療薬の開発に直結する可能性もあると考えられる。
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