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血清代谢组学揭示了肝癌和慢性肝病中脂肪酸代谢的失调。

Serum metabolomics reveals the deregulation of fatty acids metabolism in hepatocellular carcinoma and chronic liver diseases.

机构信息

CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China.

出版信息

Anal Bioanal Chem. 2012 Apr;403(1):203-13. doi: 10.1007/s00216-012-5782-4. Epub 2012 Feb 14.

Abstract

Patients with chronic liver diseases (CLD) including chronic hepatitis B and hepatic cirrhosis (CIR) are the major high-risk population of hepatocellular carcinoma (HCC). The differential diagnosis between CLD and HCC is a challenge. This work aims to study the related metabolic deregulations in HCC and CLD to promote the discovery of the differential metabolites for distinguishing the different liver diseases. Serum metabolic profiling analysis from patients with CLD and HCC was performed using a liquid chromatography-mass spectrometry system. The acquired large amount of metabolic information was processed with the random forest-recursive feature elimination method to discover important metabolic changes. It was found that long-chain acylcarnitines accumulated, whereas free carnitine, medium and short-chain acylcarnitines decreased with the severity of the non-malignant liver diseases, accompanied with corresponding alterations of enzyme activities. However, the general changing extent was smaller in HCC than in CIR, possibly due to the special energy-consumption mechanism of tumor cells. These observations may help to understand the mechanism of HCC occurrence and progression on the metabolic level and provide information for the identification of early and differential metabolic markers for HCC.

摘要

患有慢性肝脏疾病(CLD)包括慢性乙型肝炎和肝硬化(CIR)的患者是肝细胞癌(HCC)的主要高危人群。CLD 和 HCC 的鉴别诊断是一个挑战。本工作旨在研究 HCC 和 CLD 中的相关代谢失调,以促进发现用于区分不同肝脏疾病的差异代谢物。使用液相色谱-质谱联用系统对 CLD 和 HCC 患者的血清代谢物谱进行分析。通过随机森林-递归特征消除方法处理获得的大量代谢信息,以发现重要的代谢变化。结果发现,长链酰基辅酶 A 积累,而游离肉碱、中链和短链酰基辅酶 A 随着非恶性肝病的严重程度降低,同时相应的酶活性也发生改变。然而,与 CIR 相比,HCC 的总体变化程度较小,这可能是由于肿瘤细胞的特殊能量消耗机制。这些观察结果可能有助于从代谢水平理解 HCC 发生和进展的机制,并为识别 HCC 的早期和差异代谢标志物提供信息。

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