| Aberrant Lipid Metabolism in Hepatocellular Carcinoma Revealed by Plasma Metabolomics and Lipid Profiling. | |
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MedLine Citation:
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PMID: 21900402 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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 using ultraperformance liquid chromatography-electrospray ionization-quadrupole 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 performed using ultra-performance liquid chromatography-electrospray ionization-triple quadrupole mass spectrometry (UPLC-ESI-TQMS). Using this method we found that that HCC was associated also with reduced levels of lysophosphocholines (LPC) and in 4/20 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 (GCMS), 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 GCMS for conducting metabolomic investigations that can engender new insights into cancer pathobiology. |
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Authors:
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Andrew D Patterson; Olivier Maurhofer; Diren Beyoglu; Christian Lanz; Kristopher W Krausz; Thomas Pabst; Frank J Gonzalez; Jean-Francois Dufour; Jeffrey R Idle |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-9-7 |
Journal Detail:
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Title: Cancer research Volume: - ISSN: 1538-7445 ISO Abbreviation: - Publication Date: 2011 Sep |
Date Detail:
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Created Date: 2011-9-8 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2984705R Medline TA: Cancer Res Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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NCI, NCI. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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