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乙型肝炎相关肝病进展的代谢组学分析:慢性乙型肝炎、肝硬化和肝细胞癌

Metabolomic Profiling of Hepatitis B-Associated Liver Disease Progression: Chronic Hepatitis B, Cirrhosis, and Hepatocellular Carcinoma.

作者信息

Oh Junsang, Baritugo Kei-Anne Garcia, Kim Jayoung, Park Gyubin, Han Ki Jun, Lee Sangheun, Sung Gi-Ho

机构信息

Biomedical Institute of Mycological Resource, International St. Mary's Hospital, College of Medicine, Catholic Kwandong University, Incheon 22711, Republic of Korea.

Department of Laboratory Medicine, International St. Mary's Hospital, College of Medicine, Catholic Kwandong University, Incheon 22711, Republic of Korea.

出版信息

Metabolites. 2025 Jul 29;15(8):504. doi: 10.3390/metabo15080504.

DOI:10.3390/metabo15080504
PMID:40863123
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12388518/
Abstract

The hepatitis B virus (HBV) can cause chronic hepatitis B (CHB), which can rapidly progress into fatal liver cirrhosis (CHB-LC) and hepatocellular carcinoma (CHB-HCC). In this study, we investigated metabolites associated with distinct clinical stages of HBV infection for the identification of stage-specific serum metabolite biomarkers using H-NMR-based metabolomics. A total of 64 serum metabolites were identified, among which six core discriminatory metabolites, namely isoleucine, tryptophan, histamine (for CHB), and pyruvate, TMAO, lactate (for CHB-HCC), were consistently significant across univariate and multivariate statistical analyses, including ANOVA with FDR, OPLS-DA, and VIP scoring. These metabolites were closely linked to key metabolic pathways, such as propanoate metabolism, pyruvate metabolism, and the Warburg effect. The findings suggest that these six core metabolites serve as potential stage-specific biomarkers for CHB, CHB-LC, and CHB-HCC, respectively, and offer a foundation for the future development of metabolomics-based diagnostic and therapeutic strategies.

摘要

乙型肝炎病毒(HBV)可导致慢性乙型肝炎(CHB),后者可迅速发展为致命的肝硬化(CHB-LC)和肝细胞癌(CHB-HCC)。在本研究中,我们利用基于氢核磁共振(H-NMR)的代谢组学方法,研究了与HBV感染不同临床阶段相关的代谢物,以鉴定阶段特异性血清代谢物生物标志物。共鉴定出64种血清代谢物,其中六种核心鉴别代谢物,即异亮氨酸、色氨酸、组胺(用于CHB),以及丙酮酸、氧化三甲胺、乳酸(用于CHB-HCC),在单变量和多变量统计分析中均始终具有显著性,包括采用错误发现率(FDR)的方差分析(ANOVA)、正交偏最小二乘法判别分析(OPLS-DA)和变量重要性投影(VIP)评分。这些代谢物与关键代谢途径密切相关,如丙酸代谢、丙酮酸代谢和瓦伯格效应。研究结果表明,这六种核心代谢物分别作为CHB、CHB-LC和CHB-HCC潜在的阶段特异性生物标志物,为未来基于代谢组学的诊断和治疗策略的发展奠定了基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ba6/12388518/077180b794a9/metabolites-15-00504-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ba6/12388518/31073599aa47/metabolites-15-00504-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ba6/12388518/6bfdcedad6c6/metabolites-15-00504-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ba6/12388518/2e1d5bee47fe/metabolites-15-00504-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ba6/12388518/ee91e3f9301f/metabolites-15-00504-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ba6/12388518/077180b794a9/metabolites-15-00504-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ba6/12388518/31073599aa47/metabolites-15-00504-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ba6/12388518/6bfdcedad6c6/metabolites-15-00504-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ba6/12388518/2e1d5bee47fe/metabolites-15-00504-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ba6/12388518/ee91e3f9301f/metabolites-15-00504-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ba6/12388518/077180b794a9/metabolites-15-00504-g005.jpg

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本文引用的文献

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Dig Dis Sci. 2024 Jul;69(7):2488-2501. doi: 10.1007/s10620-024-08446-1. Epub 2024 Apr 23.
2
The Role of Mass Spectrometry in Hepatocellular Carcinoma Biomarker Discovery.质谱分析法在肝细胞癌生物标志物发现中的作用
Metabolites. 2023 Oct 8;13(10):1059. doi: 10.3390/metabo13101059.
3
Dysregulation of lipid metabolism in the pseudolobule promotes region-specific autophagy in hepatitis B liver cirrhosis.
假小叶内脂质代谢失调促进乙型肝炎肝硬化的区域特异性自噬。
Hepatol Commun. 2023 Jul 24;7(8). doi: 10.1097/HC9.0000000000000187. eCollection 2023 Aug 1.
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Metabolomics in hepatocellular carcinoma: From biomarker discovery to precision medicine.肝细胞癌中的代谢组学:从生物标志物发现到精准医学。
Front Med Technol. 2023 Jan 4;4:1065506. doi: 10.3389/fmedt.2022.1065506. eCollection 2022.
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Genome-Scale Metabolic Modeling Reveals Sequential Dysregulation of Glutathione Metabolism in Livers from Patients with Alcoholic Hepatitis.基因组尺度代谢模型揭示酒精性肝炎患者肝脏中谷胱甘肽代谢的顺序失调
Metabolites. 2022 Nov 22;12(12):1157. doi: 10.3390/metabo12121157.
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Evaluation of Amino Acids Profile as Non-Invasive Biomarkers of Hepatocellular Carcinoma in Egyptians.埃及人中氨基酸谱作为肝细胞癌非侵入性生物标志物的评估
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Cancer Cell Int. 2022 Nov 24;22(1):366. doi: 10.1186/s12935-022-02775-9.
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The Emerging Role of Branched-Chain Amino Acids in Liver Diseases.支链氨基酸在肝脏疾病中的新作用
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