The analysis of bile-derived exosomes to discover novel biomarkers for biliary diseases

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K08291
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Nagoya City University
• Principal Investigator: Yoshida Michihiro 名古屋市立大学, 医薬学総合研究院(医学), 講師 (20636328)
• Co-Investigator(Kenkyū-buntansha): 志村 貴也 名古屋市立大学, 医薬学総合研究院(医学), 准教授 (90405192)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 胆汁リキッドバイオプシー / 胆汁中エクソソーム / miRNA

Outline of Final Research Achievements

This study performed a global investigation of exosomal miRNAs in bile to identify potential biomarkers for biliary tract cancers (BTCs). 88 bile samples collected during endoscopic retrograde cholangiopancreatography (45 BTC and 43 noncancer control samples) were enrolled in this study. Exosomes in bile and serum samples (n=20) were collected and exosomal miRNA expression profiles were evaluated using comprehensive miRNA microarray analysis (3D-Gene). For validation, exosomal miRNA in the bile samples (n=68) were evaluated using 3D-Gene. In the discovery set, eight exosomal miRNAs in bile were identified as significant aberrant expression markers, while no miRNA with aberrant expression in serum was identified. In a comparison of the discovery and validation sets, miR-451a and miR-3619-3p were identified as reproducible upregulated markers. In addition, high miR-3619-3p expression in bile reflects poorer prognosis of BTCs.

Free Research Field

消化器内科

Academic Significance and Societal Importance of the Research Achievements

診断に難渋する胆道疾患において全く新しいアプローチによる診断方法の樹立が望まれるなか、今回エクソソーム内miRNAの網羅的解析により、血清では同定できない胆道癌特異マーカーが胆汁で同定され、miR-451aとmiR-3619-3pが胆道癌の診断マーカーとして確認された。さらに、miR-3619-3pは予後予測マーカーとしても有望であることが判明した。我々内視鏡医にこそ採取可能な胆汁を用いて解析することで、胆道疾患においては血清を上回るリキッドバイオプシーの意義が期待される。この研究は今後も継続し、さらに対象疾患を広げて解析が進み、臨床応用されることを目指す。