Metabolic Characterization of Hepatocellular Carcinoma Using Nontargeted Tissue Metabolomics

被引：380

作者：

Huang, Qiang ^{[1
]}

Tan, Yexiong ^{[2
]}

Yin, Peiyuan ^{[1
]}

Ye, Guozhu ^{[1
]}

Gao, Peng ^{[1
]}

Lu, Xin ^{[1
]}

Wang, Hongyang ^{[2
]}

Xu, Guowang ^{[1
]}

机构：

[1] Chinese Acad Sci, Dalian Inst Chem Phys, CAS Key Lab Separat Sci Analyt Chem, Dalian 116023, Peoples R China

[2] Second Mil Med Univ, Int Cooperat Lab Signal Transduct, Eastern Hepatobiliary Surg Inst, Shanghai, Peoples R China

来源：

CANCER RESEARCH | 2013年 / 73卷 / 16期

基金：

中国国家自然科学基金;

关键词：

MASS-SPECTROMETRY; COLORECTAL-CANCER; PRIMARY LIVER; METABONOMICS; EXPRESSION; BIOMARKERS; GLUTAMINE; COLON;

D O I：

10.1158/0008-5472.CAN-13-0308

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：4992 / 5002

页数：11

共 38 条

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