Development of NAFLD patient prognosis prediction method using glycan biomarkers and elucidation of its biological significance
| Project/Area Number |
20K08383
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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 53010:Gastroenterology-related
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| Research Institution | Osaka University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
三善 英知 大阪大学, 大学院医学系研究科, 教授 (20322183)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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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 | NAFLD / 予後予測バイオマーカー / 非侵襲的診断法 / マウスSWE / Mac-2 binding protein / 肝癌 / 非代償性肝硬変 / 出血性静脈瘤 / 肝関連疾患 / 大腸癌 / 予後調査 / 糖鎖バイオマーカー / 糖鎖遺伝子改変マウス / shear wave elastography / Mac-2bp / フコシル化 / 予後 |
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| Outline of Research at the Start |
申請者らは糖鎖関連バイオマーカー（Mac-2 binding protein: Mac-2bp、フコシル化ハプトグロビン: Fuc-Hpt）がNAFLDバイオマーカーとなることを明らかとし、組織診断を行ったNAFLD患者510例、健診受診患者2122例の糖鎖バイオマーカー値測定を行ってきた。これらは測定後10～15年経過した症例が大多数を占める。本研究では糖鎖関連バイオマーカー測定症例の予後調査を行い、糖鎖関連バイオマーカー値とその予後との関連について検討を行う。また基礎検討により、Mac-2bpとフコシル化のNAFLD病態進展における生物学的意義を解明していく。
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| Outline of Final Research Achievements |
We examined 353 NAFLD patients who underwent liver biopsy for which Mac-2 binding protein (M2BP) had been measured. During the average observation period of 2716 days, 8 cases of liver cancer, 11 cases of decompensated cirrhosis, 8 cases of hemorrhagic varices, and 24 cases of other organ cancers developed. They were divided into two groups (high-value group, low-value group) according to the median value of M2BP (1.603 μg/mL). The incidence of liver cancer was 8 in the high-value group, no incidence in the low-value group, and a significantly higher rate in the high-value group. The incidence of liver disease-related events was significantly higher in the high value group. The incidence of colorectal cancer was high in the high-value group (5 cases), and there were no cases in the low-value group, indicating a significant tendency. In basic research, we were able to establish a method for performing shear wave elastography using ultrasonography in mice.
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| Academic Significance and Societal Importance of the Research Achievements |
NAFLDは世界中で増加している最大の慢性肝疾患である。肝癌をはじめ、肝関連疾患発症の病因として重要な位置を占めているが、いまだサーベイランス法が確立していないのが課題である。我々が見いだしたNAFLDのバイオマーカーであるM2BPが本研究により、肝関連疾患発症、大腸癌発症の予後予測にも有用であることが明らかとなった。単一バイオマーカーで診断・予後予測マーカーとして使用可能であるM2BPを見いだした学術的・社会的意義は大きい。基礎研究ではマウスのSWE手法を確立できた。今後の基礎研究において動物愛護の観点からも非侵襲的に肝線維化を評価できる手法を開発したことは学術的意義が高い。
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Report
(4 results)
Research Products
(91 results)
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[Journal Article] Serum Mac-2 binding protein level predicts the development of liver-related events and colorectal cancer in patients with NAFLD.2022
Author(s)
Kamada Y, Nakahara T, Munekage K, Fujii H, Sawai Y, Doi Y, Ono M, Hyogo H, Sumida Y, Morishita K, Asuka T, Ouchida T, Imai Y, Miyoshi E; Japan Study Group of NAFLD.
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Journal Title
Hepatol Commun.
Volume: 6
Issue: 7
Pages: 1527-1536
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Characterization of Nutrient Intake in Biopsy-Confirmed NAFLD Patients2022
Author(s)
Kamada Y, Takahashi H, Ogawa Y, Hyogo H, Nakamura K, Yada T, Asada N, Bando T, Sawano H, Hatanaka M, Tosa T, Ando M, Hikita E, Yoshida K, Koseki M, Sumida Y, Maeda K, Fujii M, Aishima S, Hayakawa M, Nakajima A.
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Journal Title
Nutrients
Volume: 14
Issue: 17
Pages: 3453-3453
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Serum Mac-2 binding protein level predicts the development of liver-related events and colorectal cancer in patients with nonalcoholic fatty liver disease.2022
Author(s)
Kamada Y, Nakahara T, Munekage K, Fujii H, Sawai Y, Doi Y, Ono M, Hyogo H, Sumida Y, Morishita K, Asuka T, Ouchida T, Imai Y, and Miyoshi E; Japan Study Group of NAFLD (JSG-NAFLD)
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Journal Title
Hepatology Communications
Volume: in press
Related Report
Peer Reviewed
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[Journal Article] Transcriptomics Identify Thrombospondin-2 as a Biomarker for Nonalcoholic Steatohepatitis and Advanced Liver Fibrosis2021
Author(s)
Kozumi K, Kodama T, Murai H, Sakane S, Govaere O, Cockell S, Motooka D, Kakita N, Yamada Y, Kondo Y, Tahata Y, Yamada R, Hikita H, Sakamori R, Kamada Y, Daly KA, Anstee MQ, Tatsumi T, Morii E, Takehara T
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Journal Title
Hepatology
Volume: 74(5)
Issue: 5
Pages: 2452-2466
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] FIB-4 First in the Diagnostic Algorithm of Metabolic-Dysfunction-Associated Fatty Liver Disease in the Era of the Global Metabodemic2021
Author(s)
Sumida Y, Yoneda M, Tokushige K, Kawanaka M, Fujii H, Yoneda M, Imajo K, Takahashi H, Eguchi Y, Ono M, Nozaki Y, Hyogo H, Koseki M, Yoshida Y, Kawaguchi T, Kamada Y, Okanoue T, Nakajima A, Japan Study Group of NAFLD (JSG-NAFLD)
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Journal Title
Life
Volume: 11
Issue: 2
Pages: 143-143
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Dietary oxysterol, 7-Ketocholesterol accelerates hepatic lipid accumulation and macrophage infiltration in obese Mice2021
Author(s)
J. Chang, M. oseki, A. Saga, K. Kanno, T. Higo, D. Okuzaki, T. Okada, H. Inui, K. Tanaka, M. Asaji, Y. Zhu, K. Yamada, M. Ono, T. Saibara, I Ichi, T. Ohama, M. Nishida, S. Yamashita, Y. Sakata
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Journal Title
Front Endocrinol (Lausanne)
Volume: 11
Pages: 614692-614692
DOI
Related Report
Peer Reviewed / Open Access
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