Document Detail


Aberrant lipid metabolism in hepatocellular carcinoma revealed by plasma metabolomics and lipid profiling.
MedLine Citation:
PMID:  21900402     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
There has been limited analysis of the effects of hepatocellular carcinoma (HCC) on liver metabolism and circulating endogenous metabolites. Here, we report the findings of a plasma metabolomic investigation of HCC patients by ultraperformance liquid chromatography-electrospray ionization-quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOFMS), random forests machine learning algorithm, and multivariate data analysis. Control subjects included healthy individuals as well as patients with liver cirrhosis or acute myeloid leukemia. We found that HCC was associated with increased plasma levels of glycodeoxycholate, deoxycholate 3-sulfate, and bilirubin. Accurate mass measurement also indicated upregulation of biliverdin and the fetal bile acids 7α-hydroxy-3-oxochol-4-en-24-oic acid and 3-oxochol-4,6-dien-24-oic acid in HCC patients. A quantitative lipid profiling of patient plasma was also conducted by ultraperformance liquid chromatography-electrospray ionization-triple quadrupole mass spectrometry (UPLC-ESI-TQMS). By this method, we found that HCC was also associated with reduced levels of lysophosphocholines and in 4 of 20 patients with increased levels of lysophosphatidic acid [LPA(16:0)], where it correlated with plasma α-fetoprotein levels. Interestingly, when fatty acids were quantitatively profiled by gas chromatography-mass spectrometry (GC-MS), we found that lignoceric acid (24:0) and nervonic acid (24:1) were virtually absent from HCC plasma. Overall, this investigation illustrates the power of the new discovery technologies represented in the UPLC-ESI-QTOFMS platform combined with the targeted, quantitative platforms of UPLC-ESI-TQMS and GC-MS for conducting metabolomic investigations that can engender new insights into cancer pathobiology.
Authors:
Andrew D Patterson; Olivier Maurhofer; Diren Beyoglu; Christian Lanz; Kristopher W Krausz; Thomas Pabst; Frank J Gonzalez; Jean-François Dufour; Jeffrey R Idle
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-09-07
Journal Detail:
Title:  Cancer research     Volume:  71     ISSN:  1538-7445     ISO Abbreviation:  Cancer Res.     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-01     Completed Date:  2012-01-09     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  6590-600     Citation Subset:  IM    
Copyright Information:
©2011 AACR.
Affiliation:
Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Carcinoma, Hepatocellular / blood*
Chromatography, Liquid
Esters / blood
Fatty Acids, Nonesterified / blood
Female
Gas Chromatography-Mass Spectrometry
Hemochromatosis / blood
Humans
Leukemia, Myeloid, Acute / blood
Lipid Metabolism*
Lipids / blood
Liver Diseases / blood
Liver Function Tests
Liver Neoplasms / blood*
Lysophosphatidylcholines / blood
Male
Metabolomics / methods*
Middle Aged
PPAR alpha / physiology
Spectrometry, Mass, Electrospray Ionization
Grant Support
ID/Acronym/Agency:
U01 ES016013/ES/NIEHS NIH HHS; U19 AI067773-05/AI/NIAID NIH HHS; U19 AI067773-06/AI/NIAID NIH HHS; Z99 CA999999/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Esters; 0/Fatty Acids, Nonesterified; 0/Lipids; 0/Lysophosphatidylcholines; 0/PPAR alpha
Comments/Corrections

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