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Abstract：
BACKGROUND: A distinct serum metabonomic pattern has been previously revealed to be associated with various forms of liver disease. Here, we aimed to apply mass spectrometry to obtain serum metabolomic profiles from individuals with cholangiocarcinoma and benign hepatobiliary diseases to gain an insight into pathogenesis and search for potential early-disease biomarkers.
METHODS: Serum samples were profiled using a hydrophilic interaction liquid chromatography platform, coupled to a mass spectrometer. A total of 47 serum specimens from 8 cholangiocarcinoma cases, 20 healthy controls, 8 benign disease controls (bile duct strictures) and 11 patients with hepatocellular carcinoma (as malignant disease controls) were included. Data analysis was performed using univariate and multivariate statistics.
RESULTS: The serum metabolome disparities between the metabolite profiles from healthy controls and patients with hepatobiliary disease were predominantly related to changes in lipid and lipid-derived compounds (phospholipids, bile acids and steroids) and amino acid metabolites (phenylalanine). A metabolic pattern indicative of inflammatory response due to cirrhosis and cholestasis was associated with the disease groups. The abundance of phospholipid metabolites was altered in individuals with liver disease, particularly cholangiocarcinoma, but no significant difference was seen between profiles from patients with benign biliary strictures and cholangiocarcinoma.
CONCLUSIONS: The serum metabolome in cholangiocarcinoma exhibited changes in metabolites related to inflammation, altered energy production and phospholipid metabolism. This study serves to highlight future avenues for biomarker research in large-scale studies.
METHODS: Serum samples were profiled using a hydrophilic interaction liquid chromatography platform, coupled to a mass spectrometer. A total of 47 serum specimens from 8 cholangiocarcinoma cases, 20 healthy controls, 8 benign disease controls (bile duct strictures) and 11 patients with hepatocellular carcinoma (as malignant disease controls) were included. Data analysis was performed using univariate and multivariate statistics.
RESULTS: The serum metabolome disparities between the metabolite profiles from healthy controls and patients with hepatobiliary disease were predominantly related to changes in lipid and lipid-derived compounds (phospholipids, bile acids and steroids) and amino acid metabolites (phenylalanine). A metabolic pattern indicative of inflammatory response due to cirrhosis and cholestasis was associated with the disease groups. The abundance of phospholipid metabolites was altered in individuals with liver disease, particularly cholangiocarcinoma, but no significant difference was seen between profiles from patients with benign biliary strictures and cholangiocarcinoma.
CONCLUSIONS: The serum metabolome in cholangiocarcinoma exhibited changes in metabolites related to inflammation, altered energy production and phospholipid metabolism. This study serves to highlight future avenues for biomarker research in large-scale studies.
摘要：
背景：先前已发现一种独特的血清代谢组学模式与各种形式的肝病有关。这里,我们旨在应用质谱技术从胆管癌和良性肝胆疾病患者中获取血清代谢组学谱,以深入了解发病机制并寻找潜在的早期疾病生物标志物.
方法：使用亲水相互作用液相色谱平台对血清样品进行分析，耦合到质谱仪。共收集8例胆管癌患者的47份血清标本，20个健康对照，包括8例良性疾病对照（胆管狭窄）和11例肝细胞癌患者（作为恶性疾病对照）。使用单变量和多变量统计进行数据分析。
结果：来自健康对照组和肝胆疾病患者的代谢物谱之间的血清代谢组差异主要与脂质和脂质衍生化合物的变化有关（磷脂，胆汁酸和类固醇）和氨基酸代谢物（苯丙氨酸）。表明肝硬化和胆汁淤积引起的炎症反应的代谢模式与疾病组相关。磷脂代谢物的丰度在肝病患者中发生了改变，尤其是胆管癌,但是良性胆管狭窄和胆管癌患者的轮廓之间没有显着差异。
结论：胆管癌的血清代谢组表现出与炎症相关的代谢产物的变化，改变能量产生和磷脂代谢。这项研究旨在突出大规模研究中生物标志物研究的未来途径。
方法：使用亲水相互作用液相色谱平台对血清样品进行分析，耦合到质谱仪。共收集8例胆管癌患者的47份血清标本，20个健康对照，包括8例良性疾病对照（胆管狭窄）和11例肝细胞癌患者（作为恶性疾病对照）。使用单变量和多变量统计进行数据分析。
结果：来自健康对照组和肝胆疾病患者的代谢物谱之间的血清代谢组差异主要与脂质和脂质衍生化合物的变化有关（磷脂，胆汁酸和类固醇）和氨基酸代谢物（苯丙氨酸）。表明肝硬化和胆汁淤积引起的炎症反应的代谢模式与疾病组相关。磷脂代谢物的丰度在肝病患者中发生了改变，尤其是胆管癌,但是良性胆管狭窄和胆管癌患者的轮廓之间没有显着差异。
结论：胆管癌的血清代谢组表现出与炎症相关的代谢产物的变化，改变能量产生和磷脂代谢。这项研究旨在突出大规模研究中生物标志物研究的未来途径。
