Metabolic Characterization of Hepatocellular Carcinoma Using Nontargeted Tissue Metabolomics
Metabolic Characterization of Hepatocellular Carcinoma Using Nontargeted Tissue Metabolomics
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使用非靶向组织代谢组学表征肝细胞癌的代谢特征
DOI：
10.1158/0008-5472.can-13-0308
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发表时间：
2013-08-15
期刊：
影响因子：
11.2
通讯作者：
Xu, Guowang
中科院分区：
文献类型：
--
作者：
Huang, Qiang;Tan, Yexiong;Xu, Guowang
肝细胞癌由于发展快、转移早，预后较差。在本报告中，我们使用基于液相色谱-质谱法的非靶向代谢分析策略来表征肝细胞癌的代谢特征。从肝细胞癌患者身上收集了 50 对肝癌样本和匹配的正常组织，包括肿瘤组织、癌旁非癌组织和远端非癌组织，从组织代谢组中筛选并鉴定了 105 种代谢物。 HCC 肿瘤中的主要代谢变化包括糖酵解、糖异生和 β-氧化升高，同时三羧酸循环和 Delta-12 去饱和酶减少。此外，还观察到谷胱甘肽和其他抗氧化分子的水平升高，同时与炎症相关的多不饱和脂肪酸和磷脂酶 A2 的水平降低。对来自慢性肝炎、肝硬化和肝细胞癌患者的 298 份血清标本进行了组织中的差异代谢水平检测。甜菜碱和丙酰肉碱被证实具有良好的诊断潜力，可区分肝细胞癌与慢性肝炎和肝硬化。肝硬化和肝细胞癌血清标本的外部验证进一步表明，该组合生物标志物可用于诊断肝细胞癌，并具有甲胎蛋白的补充作用。 (C) 2013 年 AACR。
Hepatocellular carcinoma has a poor prognosis due to its rapid development and early metastasis. In this report, we characterized the metabolic features of hepatocellular carcinoma using a nontargeted metabolic profiling strategy based on liquid chromatography-mass spectrometry. Fifty pairs of liver cancer samples and matched normal tissues were collected from patients having hepatocellular carcinoma, including tumor tissues, adjacent noncancerous tissues, and distal noncancerous tissues, and 105 metabolites were filtered and identified from the tissue metabolome. The principal metabolic alternations in HCC tumors included elevated glycolysis, gluconeogenesis, and beta-oxidation with reduced tricarboxylic acid cycle and Delta-12 desaturase. Furthermore, increased levels of glutathione and other antioxidative molecules, together with decreased levels of inflammatory-related polyunsaturated fatty acids and phospholipase A2, were observed. Differential metabolite levels in tissues were tested in 298 serum specimens from patients with chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Betaine and propionylcarnitine were confirmed to confer good diagnostic potential to distinguish hepatocellular carcinoma from chronic hepatitis and cirrhosis. External validation of cirrhosis and hepatocellular carcinoma serum specimens further showed that this combination biomarker is useful for diagnosis of hepatocellular carcinoma with a supplementary role to alpha-fetoprotein. (C) 2013 AACR.