| Project/Area Number |
20K10475
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 58030:Hygiene and public health-related: excluding laboratory approach
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| Research Institution | Osaka Metropolitan University (2022-2024)
Osaka City University (2020-2021) |
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Principal Investigator |
Koh Hideo 大阪公立大学, 大学院医学研究科, 講師 (90419698)
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| Co-Investigator(Kenkyū-buntansha) |
波江野 洋 東京理科大学, 研究推進機構生命医科学研究所, 准教授 (70706754)
中前 博久 大阪公立大学, 大学院医学研究科, 准教授 (30364003)
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| Project Period (FY) |
2020-04-01 – 2025-03-31
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| Project Status |
Completed (Fiscal Year 2024)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 分子疫学 / 同種造血幹細胞移植 / 重症消化管GVHD / 重症皮膚GVHD / 非侵襲的診断法 / 血液悪性腫瘍 / エクソソーム / マイクロRNA / 数理モデリング |
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| Outline of Research at the Start |
本研究では、移植患者の前向きコホート200例の保存検体と臨床データを用い、末梢血中の microRNAの網羅的解析により、再発、GVHDなど予後に関わる重要アウトカムの予測法の確立および治療標的となり得る新規分子の探索、同定を目的とする。また、症例集積中の血液疾患コホートを用い、数理モデリングによる病態解析を試みる。
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| Outline of Final Research Achievements |
This study involved two cohorts and yielded the following findings:(1) In the retrospective cohort, the impact of donor NKG2D gene polymorphism rs1049174 on relapse risk in HLA-haploidentical transplantation using post-transplant cyclophosphamide (PTCy) was examined. Results indicated that when anti-thymocyte globulin (ATG) was not used, transplantation from donors with the CC genotype was associated with a reduced relapse risk and improved survival in non-AML patients. (2) In the prospective cohort, comprehensive microRNA (miRNA) expression analysis in whole serum and serum exosomes at GVHD onset was performed using microarrays. A 22-miRNA profile in serum exosomes showed high predictive accuracy for severe gut GVHD (ROC AUC: 0.94; diagnostic accuracy: 95.8%). Another 22-miRNA profile specific to severe skin GVHD yielded a ROC AUC of 0.81 and diagnostic accuracy of 83.3%. Conversely, no miRNAs capable of discriminating either severe gut or skin GVHD were identified in whole serum.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は、ドナーNKG2D遺伝子多型が同種移植後の再発リスクに影響することを明らかにし、個別化されたドナー選定への応用可能性を示した。また、重症消化管GVHDおよび重症皮膚GVHDの高精度な非侵襲的診断が可能な血清エクソソーム中マイクロRNAプロファイルを同定し、早期診断や重症化予防への貢献が期待される。
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