Document Detail


Serum and urine metabolite profiling reveals potential biomarkers of human hepatocellular carcinoma.
MedLine Citation:
PMID:  21518826     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Hepatocellular carcinoma (HCC) is a common malignancy in the world with high morbidity and mortality rate. Identification of novel biomarkers in HCC remains impeded primarily because of the heterogeneity of the disease in clinical presentations as well as the pathophysiological variations derived from underlying conditions such as cirrhosis and steatohepatitis. The aim of this study is to search for potential metabolite biomarkers of human HCC using serum and urine metabolomics approach. Sera and urine samples were collected from patients with HCC (n = 82), benign liver tumor patients (n = 24), and healthy controls (n = 71). Metabolite profiling was performed by gas chromatography time-of-flight mass spectrometry and ultra performance liquid chromatography-quadrupole time of flight mass spectrometry in conjunction with univariate and multivariate statistical analyses. Forty three serum metabolites and 31 urinary metabolites were identified in HCC patients involving several key metabolic pathways such as bile acids, free fatty acids, glycolysis, urea cycle, and methionine metabolism. Differentially expressed metabolites in HCC subjects, such as bile acids, histidine, and inosine are of great statistical significance and high fold changes, which warrant further validation as potential biomarkers for HCC. However, alterations of several bile acids seem to be affected by the condition of liver cirrhosis and hepatitis. Quantitative measurement and comparison of seven bile acids among benign liver tumor patients with liver cirrhosis and hepatitis, HCC patients with liver cirrhosis and hepatitis, HCC patients without liver cirrhosis and hepatitis, and healthy controls revealed that the abnormal levels of glycochenodeoxycholic acid, glycocholic acid, taurocholic acid, and chenodeoxycholic acid are associated with liver cirrhosis and hepatitis. HCC patients with alpha fetoprotein values lower than 20 ng/ml was successfully differentiated from healthy controls with an accuracy of 100% using a panel of metabolite markers. Our work shows that metabolomic profiling approach is a promising screening tool for the diagnosis and stratification of HCC patients.
Authors:
Tianlu Chen; Guoxiang Xie; Xiaoying Wang; Jia Fan; Yunping Qiu; Xiaojiao Zheng; Xin Qi; Yu Cao; Mingming Su; Xiaoyan Wang; Lisa X Xu; Yun Yen; Ping Liu; Wei Jia
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-04-25
Journal Detail:
Title:  Molecular & cellular proteomics : MCP     Volume:  10     ISSN:  1535-9484     ISO Abbreviation:  Mol. Cell Proteomics     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-07-11     Completed Date:  2011-10-21     Revised Date:  2011-12-12    
Medline Journal Info:
Nlm Unique ID:  101125647     Medline TA:  Mol Cell Proteomics     Country:  United States    
Other Details:
Languages:  eng     Pagination:  M110.004945     Citation Subset:  IM    
Affiliation:
Ministry of Education Key Laboratory of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Aged
Bile Acids and Salts / blood,  urine
Carcinoma, Hepatocellular / blood*,  diagnosis,  urine
Case-Control Studies
Female
Humans
Liver Neoplasms / blood*,  diagnosis,  urine
Male
Metabolome*
Middle Aged
Neoplasm Staging
Principal Component Analysis
Tumor Markers, Biological / blood*,  urine
Young Adult
alpha-Fetoproteins / metabolism,  urine
Chemical
Reg. No./Substance:
0/Bile Acids and Salts; 0/Tumor Markers, Biological; 0/alpha-Fetoproteins
Comments/Corrections
Erratum In:
Mol Cell Proteomics. 2011 Nov;10(11). doi:10.1074/mcp.A110.004945

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