2023 Fiscal Year Final Research Report

Development of liquid biopsy technology (donor-derived DNA analysis) aimed at improving the results of liver transplantation

Research Project

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Project/Area Number	20K08967
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 55010:General surgery and pediatric surgery-related
Research Institution	International University of Health and Welfare
Principal Investigator	Shinoda Masahiro 国際医療福祉大学, 医学部消化器外科, 教授 (50286499)
Co-Investigator(Kenkyū-buntansha)	井ノ上逸朗国立遺伝学研究所, ゲノム・進化研究系, 教授 (00192500) 日比泰造熊本大学, 大学院生命科学研究部(医), 教授 (10338072) 山田洋平慶應義塾大学, 医学部(信濃町), 講師 (60383816) 河地茂行東京医科大学, 医学部, 主任教授 (80234079) 高原武志藤田医科大学, 医学部, 教授 (80453306)
Project Period (FY)	2020-04-01 – 2024-03-31
Keywords	リキッドバイオプシー / 拒絶反応 / 肝移植
Outline of Final Research Achievements	To evaluate the use of donor‐derived cell‐free DNA (dd‐cfDNA) in diagnosing　graft injuries in Japanese liver transplantation (LTx).　A total of 321 samples from 10 newly operated LTx recipients were　collected. Fifty‐five　samples from 55 recipients were collected during protocol biopsies (PB), whereas　36 samples from 27 recipients were collected during event biopsies, consisting of 11　biopsy‐proven acute rejection (AR), 20 acute dysfunctions without rejection　(ADWR), and 5 chronic rejections. The dd‐cfDNA levels were elevated significantly after LTx. The dd‐cfDNA levels were significantly higher in the 11 samples obtained　during AR than those obtained during PB. The ROC curve analysis of diagnostic　ability yielded areas under the curve of 0.975 for AR versus PB. The dd‐cfDNA levels　during AR were elevated earlier and correlated more strongly with the RAI　than AST/ALT. Donor‐derived cell‐free DNA serves as a sensitive biomarker for　detecting graft injuries in LTx.
Free Research Field	移植医療
Academic Significance and Societal Importance of the Research Achievements	今回われわれは肝臓移植後患者を対象とした研究で，日本で初めてとなるドナー由来cell free DNAに関する研究を行った。肝移植における急性拒絶反応の診断にドナー由来遊離DNA（dd-cfDNA）の検出が有用である可能性が示唆され、本法が臨床的に応用されれば従来の侵襲的経皮的肝生検の代わりにリキッドバイオプシーで非侵襲的に拒絶を診断できる可能性がある。また、心、肺、腎、小腸、膵など多臓器に応用し有用性を示すことができれば社会的意義は絶大となる。