Serum Metabolic Profiling Study of Hepatocellular Carcinoma Infected with Hepatitis B or Hepatitis C Virus by Using Liquid Chromatography-Mass Spectrometry
Serum Metabolic Profiling Study of Hepatocellular Carcinoma Infected with Hepatitis B or Hepatitis C Virus by Using Liquid Chromatography-Mass Spectrometry
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乙型肝炎或丙型肝炎病毒感染的肝细胞癌的液相色谱-质谱联用法研究
DOI：
10.1021/pr300683a
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发表时间：
2012-11-01
影响因子：
4.4
通讯作者：
Xu, Guowang
中科院分区：
文献类型：
--
作者：
Zhou, Lina;Ding, Lili;Xu, Guowang
本研究的目的是探讨乙型肝炎病毒（HBV）或丙型肝炎病毒（HCV）感染的肝细胞癌（HCC）的共同和特异性代谢改变。血清分析数据显示，两组HCC患者的代谢谱主要相似，为研究其共同的肿瘤发病机制和早期诊断生物标志物提供了基础。与肝硬化和健康对照组相比，花生四烯酸在HCC组中作为促炎前体显著增加。具有强抗炎活性的多不饱和脂肪酸酰基链溶血磷脂酰胆碱（lysoPCs）在HCC和肝硬化组与健康对照组相比显著降低，这可能与维持慢性炎症有关，有利于肝恶性肿瘤的发生和发展。与感染HBV或HCV的慢性肝病和健康对照组相比，HCC组中多不饱和溶血opcs与饱和溶血opcs的比例降低，进一步表明肝脏恶性肿瘤具有独立于病毒感染的深远影响。特别是，HCC组血清内源性大麻素anandamide （AEA）和棕榈乙醇酰胺（PEA）与健康对照组相比显著升高，HCC合并HCV与相应的慢性肝病相比显著升高。AEA、PEA或两者联合用于区分HCC与慢性肝病的敏感性、特异性和曲线下面积均较好，是区分HCC与丙肝肝硬化的潜在生物标志物。
The objective of the present study was to explore the common and specific metabolic alterations of hepatocellular carcinoma (HCC) infected with hepatitis B virus (HBV) or hepatitis C virus (HCV). Serum profiling data revealed that the two HCC groups shared a mainly similar metabolic profile, providing a basis for investigating their common tumor pathogenesis mechanism and early diagnosis biomarkers. Arachidonic acid as a pro-inflammatory precursor increased significantly in the HCC group compared to the cirrhosis and healthy control. And the lysophosphatidylcholines (lysoPCs) with polyunsaturated fatty acid acyl chain with potent anti-inflammatory activity significantly decreased in the HCC and cirrhosis groups compared to those in the healthy control group, which may partly contribute to maintaining chronic inflammation and benefit the initiation and progression of the malignant hepatic tumor. The decreased ratios of polyunsaturated lysoPCs to saturated lysoPCs in HCC groups compared to chronic liver diseases infected with HBV or HCV and healthy control further demonstrated that a malignant liver tumor exerts profound influences independent of virus infection. Especially, serum endocannabinoids anandamide (AEA) and palmitylethanolamide (PEA) were found significantly elevated in HCC groups compared to healthy control, and in HCC with HCV compared to corresponding chronic liver diseases. AEA, PEA, or their combination showed better sensitivity, specificity, and the area under the curve for distinguishing HCC from chronic liver diseases, showing they are potential biomarkers to distinguish the HCC from cirrhosis infected with HCV.