A serum metabonomic study on the difference between alcohol- and HBV-induced liver cirrhosis by ultraperformance liquid chromatography coupled to mass spectrometry plus quadrupole time-of-flight mass spectrometry
A serum metabonomic study on the difference between alcohol- and HBV-induced liver cirrhosis by ultraperformance liquid chromatography coupled to mass spectrometry plus quadrupole time-of-flight mass spectrometry
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DOI：
10.3760/cma.j.issn.0366-6999.2011.09.018
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发表时间：
2011-05-05
影响因子：
6.1
通讯作者：
Huang Jian-rong
中科院分区：
文献类型：
--
作者：
Lian Jiang-shan;Liu Wei;Huang Jian-rong
肝硬化是慢性肝炎的致命后果，肝硬化的早期诊断至关重要。肝活检仍然是肝硬化的标准诊断方法，尽管它在酒精中毒或B型肝炎病毒（HBV）感染的广泛人群中的应用仍然很困难。在这项研究中，我们使用代谢组学方法来检测早期诊断肝硬化的潜在生物标志物。方法前瞻性收集正常对照组（n=22）、酒精性肝硬化（n=18）或乙型肝炎肝硬化（n=19）患者的血清样本。采用超高效液相色谱（LC）/飞行时间质谱（MS）结合化学计量学分析血清代谢物组。采用主成分分析（PCA）和偏最小二乘判别分析（PLS-DA）对LC-MS数据进行归一化处理。肝硬化患者血清溶血磷脂酰胆碱（LPC）（LPC C16：0、LPC 018：0、LPC 018：2、LPC C18：3、LPC 020：3、LPC C20：5）降低，而胆汁酸（甘氨胆酸、甘氨鹅去氧胆酸）、次黄嘌呤和硬脂酰胺升高。这些代谢物被认为是肝硬化的“常见”生物标志物。油酰胺和肉豆蔻酰胺在酒精性肝硬化患者血清中升高，但在HBV诱导的肝硬化患者血清中降低。结论酒精性肝硬化与HBV性肝硬化代谢组学存在显著差异。代谢组学是一种自上而下的系统生物学工具，用于研究临床问题。中华医学杂志2011;124（9）：1367-1373
Background Liver cirrhosis is the fatal consequence of chronic hepatitis, making early diagnosis of liver cirrhosis critical. Liver biopsy is still the standard diagnostic method for liver cirrhosis, although its use in a broad population with alcoholism or hepatitis B virus (HBV) infection remains difficult. In this study, we used a metabonomic approach to detect potential biomarkers for early diagnosis of liver cirrhosis.Methods Serum specimens were collected prospectively from normal control subjects (n=22) and patients with alcoholic cirrhosis (n=18) or HBV-induced cirrhosis (n=19). The serum metabonome was analyzed using ultraperformance liquid chromatography (LC)/time-of-flight mass spectrometry (MS) integrated with chemometrics. The acquired LC-MS data were normalized and processed using principal component analysis (PCA) and partial least squares discrimination analysis (PLS-DA).Results Significant differences in the metabonomics among the three groups were observed. Lysophosphatidyl cholines (LPCs) (LPC C16:0, LPC 018:0, LPC 018:2, LPC C18:3, LPC 020:3, LPC C20:5) were decreased in the serum of patients with hepatic cirrhosis, whereas bile acids (glycocholic acid, glycochenodeoxycholic acid), hypoxanthine, and stearamide were increased in the serum of patients with hepatic cirrhosis. These metabolites are considered "common" biomarkers for hepatic cirrhosis. Oleamide and myristamide were increased in the serum of patients with alcoholic cirrhosis but decreased in those with HBV-induced cirrhosis. These could be specific biomarkers for differential diagnosis between alcohol- and HBV-induced hepatic cirrhosis.Conclusions There are significant metabonomic differences between alcohol- and HBV-induced liver cirrhosis. Metabonomics is a top-down systems biology tool for conducting research on clinical problems. Chin Med J 2011;124(9):1367-1373