Prediction of prognosis targeting microRNAs in exosomes in primary biliary cholangitis

• Project/Area Number: 18K07416
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52010:General internal medicine-related
• Research Institution: Kagawa University
• Principal Investigator: Nomura Takako 香川大学, 医学部, 協力研究員 (70645415)
• Co-Investigator(Kenkyū-buntansha): 正木 勉 香川大学, 医学部, 教授 (30335848) ; 坂本 鉄平 香川大学, 医学部, 協力研究員 (30769328) ; 藤田 浩二 香川大学, 医学部附属病院, 助教 (50749421) ; 森下 朝洋 香川大学, 医学部附属病院, 講師 (60423430) ; 米山 弘人 香川大学, 医学部附属病院, 助教 (80294750)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2018: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 原発性胆汁性胆管炎 / microRNA / 自己免疫性肝疾患

Outline of Final Research Achievements

A comprehensive analysis of microRNAs (miRNAs) in exosomes (exocellular vesicles) in the peripheral blood of patients with primary biliary cholangitis (PBC), and the biological characteristics of miRNAs that showed altered expression. We investigated the possibility that miRNAs in exosomes could serve as biomarkers and predictors of therapeutic effects for appropriate personalized treatment in the future.
In a study classified into a group with good therapeutic effect and a group with poor therapeutic effect with ursodeoxycholic acid (UDCA), 4 molecules (hsa-miR-940, hsa-miR-1470, hsa-miR-3663-3p, hsa-miR-4632-3p) were listed as a candidate.

Academic Significance and Societal Importance of the Research Achievements

PBCの第1選択薬はウルソデオキシコール酸(Ursodeoxycholic acid; UDCA)であり、UDCAに対する治療反応性が良好であれば生命予後は一般集団とほぼ同等であるが、治療反応性が不良な場合には徐々に進行して肝硬変へ至り、肝不全ないし肝細胞癌を発症する。治療開始後の早期に何らかの基準を用いてUDCAに対する治療反応性を判定し、治療反応性が不良と判断された場合には速やかにセカンドラインの治療を行うことが重要と考える。今回の研究成果が、治療開始早期の治療効果判定の一助になる可能性がある。

Research Products

• [Journal Article] Bezafibrate Improves GLOBE and UK-PBC Scores and Long-Term Outcomes in Patients With Primary Biliary Cholangitis. (2019)
  • Author(s): Honda A, Tanaka A, Kaneko T, Komori A, Abe M, Inao M, Namisaki T, Hashimoto N, Kawata K, Takahashi A, Ninomiya M, Kang JH, Arakawa M, Yamagiwa S, Joshita S, Umemura T, Sato K, Kaneko A, Kikuchi K, Itakura J, Nomura T, et.al.
  • Journal Title: Hepatology. Volume: 印刷中 Issue: 6 Pages: 2035-2046
  • DOI: 10.1002/hep.30552
  • Peer Reviewed / Open Access