| Project/Area Number |
18K15792
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 53010:Gastroenterology-related
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| Research Institution | Osaka City University |
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Principal Investigator |
Kozuka Ritsuzo 大阪市立大学, 大学院医学研究科, 病院講師 (10726657)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | B型肝炎 / 肝発癌 / エクソソーム / マイクロRNA |
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| Outline of Final Research Achievements |
We analyzed exosomal miRNA associated with progression of liver fibrosis in patients with chronic hepatitis B virus infection, and identified five miRNAs, i.e., miR-3648, miR-3665, miR-122-5p, miR-3960, and miR-4739. In addition, we analyzed miRNAs that correlate with development of hepatocellular carcinoma (HCC) in patients treated and untreated with nucleos(t)ide analogue (NA), and identified that predictive accuracy of HCC development is increased by using a combination of 22 miRNA expression patterns in patients untreated with NA. However, it was impossible to predict by using this combination in patients treated with NA. The miRNA expression pattern that predicts HCC development in patients with chronic hepatitis B virus infection differs between patients treated and untreated with NA, suggesting that NA treatment may change the mechanism of HCC development.
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| Academic Significance and Societal Importance of the Research Achievements |
B型肝炎ウイルスを完全に排除する治療法はなく、多くのB型慢性肝疾患患者に核酸アナログ(NA)治療が行われ、肝発癌をいかに抑制するかが最大の治療目標となっている。一方、肝線維化進展や肝発癌を予測できるバイオマーカーの開発が望まれるが、血清エクソソーム中のmiRNAは安定性が高く、新たなバイオマーカーとして期待される。本研究では、肝線維化進展や肝発癌と相関する血清エクソソーム中のmiRNAを同定した。また、肝発癌予測に関するmiRNA発現パターンがNA治療の有無により異なり、肝発癌メカニズムがNAで変化することが示され、NAによる肝発癌抑制の機序を明らかにしたことは学術的に意義が高いと考えられる。
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