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血清和尿液代谢组学研究骨肉瘤。

Serum and urinary metabonomic study of human osteosarcoma.

机构信息

Shanghai 10th People's Hospital, Tongji University School of Medicine, Shanghai 200072, PR China.

出版信息

J Proteome Res. 2010 Sep 3;9(9):4861-8. doi: 10.1021/pr100480r.

DOI:10.1021/pr100480r
PMID:20690664
Abstract

Osteosarcoma (OS) is the most common malignant bone tumor found in children. Currently, researchers have focused on protein and gene levels, while the associated metabolic variations have been poorly understood. In this study, we used a gas chromatography mass spectrometry approach and profiled small-molecule metabolites in serum and urine of 24 OS patients, 19 benign bone tumor patients, and 32 healthy controls, to determine whether there are significant alterations associated with carcinogenesis. The metabonomic results demonstrate clear intergroup separations between healthy control subjects and bone tumor patients in the orthogonal partial least-squares-discriminant analysis (OPLS-DA) models. Differential metabolites identified from the metabonomic analysis suggest a disrupted energy metabolism in OS patients, as characterized by significantly down-regulated TCA cycle and glycolysis, down-regulated lipid metabolism, dysregulated sugar levels, and up-regulated amino acid metabolism. Additionally, an increased activity of glutathione metabolism, and increased polyamine metabolism also contributed to a characteristic metabolic signature of OS patients.

摘要

骨肉瘤(OS)是儿童中最常见的恶性骨肿瘤。目前,研究人员主要关注蛋白质和基因水平,而相关的代谢变化则知之甚少。在这项研究中,我们使用气相色谱-质谱联用技术,对 24 例骨肉瘤患者、19 例良性骨肿瘤患者和 32 名健康对照者的血清和尿液中的小分子代谢物进行了分析,以确定是否存在与癌变相关的显著变化。代谢组学结果表明,在正交偏最小二乘判别分析(OPLS-DA)模型中,健康对照组和骨肿瘤患者之间存在明显的组间分离。代谢组学分析中鉴定的差异代谢物表明骨肉瘤患者的能量代谢受到破坏,其特征为三羧酸循环和糖酵解显著下调、脂质代谢下调、糖水平失调和氨基酸代谢上调。此外,谷胱甘肽代谢活性增加和多胺代谢增加也导致了骨肉瘤患者的特征代谢特征。

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