Abstract
Abstract Characterizing the metabolic changes pertaining to hepatocellular carcinoma (HCC) in patients with liver cirrhosis (LC) is believed to contribute towards early detection, treatment, and our understanding of the molecular mechanisms of HCC. Prospectively evaluated adult patients with LC were recruited from our hepatology practice. All patients were diagnosed to have LC on the basis of established clinical, laboratory and imaging criteria. Cases were diagnosed to have HCC based on either histology or characteristic imaging features. The LC controls were required to be HCC free for at least 6 months from the time of study entry. We compared metabolite levels in sera of 78 HCC cases with 184 LC controls by using ultra performance liquid chromatography coupled with a hybrid quadrupole time-of-flight mass spectrometry (UPLC-QTOF MS). Following data preprocessing, the most relevant ions in distinguishing HCC cases from LC controls were selected by statistical methods. Putative metabolite identifications for these ions were obtained through mass-based database search. Pathway analysis of these putative identifications reveals significant enrichment of metabolites involved in bile acid biosynthesis, porphyrin and chlorophyll metabolism, and arachidonic acid metabolism. Verification of the identities of selected metabolites was conducted by comparing their MS/MS fragmentation patterns and retention time with those from authentic compounds. Quantitation of these metabolites was performed in a subset of the serum samples (10 HCC and 10 LC) using isotope dilution by selected reaction monitoring (SRM) on triple quadrupole linear ion trap (QqQLIT) mass spectrometer. The results of this analysis confirms that metabolites involved in phospholipid catabolism such as sphingosine-1-phosphate (S-1-P) and lysophosphatidylcholine are up-regulated in sera of HCC vs. those with LC. Down-regulated metabolites include those involved in cholesterol metabolism such as glycochenodeoxycholic acid 3-sulfate (3-sulfo-GCDCA), glycocholic acid (GCA), glycodeoxycholic acid (GDCA), taurocholic acid (TCA), taurochenodeoxycholate (TCDCA), as well as those involved in heme catabolism including billuribin, I-Urobili, and bilirubin glucuronide. The preliminary results obtained in this study provide useful insights into our understanding of metabolic differences between HCC and LC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4795. doi:1538-7445.AM2012-4795
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