• 1
    Altekruse SF, McGlynn KA, Reichman ME. Hepatocellular carcinoma incidence, mortality, and survival trends in the United States from 1975 to 2005. J Clin Oncol 2009; 27: 1485-1491.
  • 2
    Perz JF, Armstrong GL, Farrington LA, Hutin YJ, Bell BP. The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide. J Hepatol 2006; 45: 529-538.
  • 3
    Forner A, Llovet JM, Bruix J. Hepatocellular carcinoma. Lancet 2012; 379: 1245-1255.
  • 4
    Lencioni R. Surveillance and early diagnosis of hepatocellular carcinoma. Dig Liver Dis 2010; 42(Suppl 3): S223-227.
  • 5
    Chen CJ, Lee MH. Early diagnosis of hepatocellular carcinoma by multiple microRNAs: validity, efficacy, and cost-effectiveness. J Clin Oncol 2011; 29: 4745-4747.
  • 6
    Forner A, Bruix J. Biomarkers for early diagnosis of hepatocellular carcinoma. Lancet Oncol 2012; 13: 750-751.
  • 7
    Beyoglu D, Idle JR. Metabolomics and its potential in drug development. Biochem Pharmacol 2013; 85: 12-20.
  • 8
    Patterson AD, Maurhofer O, Beyoglu D, Lanz C, Krausz KW, Pabst T, et al. Aberrant lipid metabolism in hepatocellular carcinoma revealed by plasma metabolomics and lipid profiling. Cancer Res 2011; 71: 6590-6600.
  • 9
    Chen T, Xie G, Wang X, Fan J, Qiu Y, Zheng X, et al. Serum and urine metabolite profiling reveals potential biomarkers of human hepatocellular carcinoma. Mol Cell Proteomics 2011; 10: M110 004945.
  • 10
    Ressom HW, Xiao JF, Tuli L, Varghese RS, Zhou B, Tsai TH, et al. Utilization of metabolomics to identify serum biomarkers for hepatocellular carcinoma in patients with liver cirrhosis. Anal Chim Acta 2012; 743: 90-100.
  • 11
    Xiao JF, Varghese RS, Zhou B, Nezami Ranjbar MR, Zhao Y, Tsai TH, et al. LC-MS based serum metabolomics for identification of hepatocellular carcinoma biomarkers in Egyptian cohort. J Proteome Res 2012; 11: 5914-5923.
  • 12
    Zhou L, Wang Q, Yin P, Xing W, Wu Z, Chen S, et al. Serum metabolomics reveals the deregulation of fatty acids metabolism in hepatocellular carcinoma and chronic liver diseases. Anal Bioanal Chem 2012; 403: 203-213.
  • 13
    Chen F, Xue J, Zhou L, Wu S, Chen Z. Identification of serum biomarkers of hepatocarcinoma through liquid chromatography/mass spectrometry-based metabonomic method. Anal Bioanal Chem 2011; 401: 1899-1904.
  • 14
    Tan Y, Yin P, Tang L, Xing W, Huang Q, Cao D, et al. Metabolomics study of stepwise hepatocarcinogenesis from the model rats to patients: potential biomarkers effective for small hepatocellular carcinoma diagnosis. Mol Cell Proteomics 2012; 11: M111 010694.
  • 15
    Wang B, Chen D, Chen Y, Hu Z, Cao M, Xie Q, et al. Metabonomic profiles discriminate hepatocellular carcinoma from liver cirrhosis by ultraperformance liquid chromatography-mass spectrometry. J Proteome Res 2012; 11: 1217-1227.
  • 16
    Yin P, Wan D, Zhao C, Chen J, Zhao X, Wang W, et al. A metabonomic study of hepatitis B-induced liver cirrhosis and hepatocellular carcinoma by using RP-LC and HILIC coupled with mass spectrometry. Mol Biosyst 2009; 5: 868-876.
  • 17
    Wu H, Xue R, Dong L, Liu T, Deng C, Zeng H, et al. Metabolomic profiling of human urine in hepatocellular carcinoma patients using gas chromatography/mass spectrometry. Anal Chim Acta 2009; 648: 98-104.
  • 18
    Ye G, Zhu B, Yao Z, Yin P, Lu X, Kong H, et al. Analysis of urinary metabolic signatures of early hepatocellular carcinoma recurrence after surgical removal using gas chromatography-mass spectrometry. J Proteome Res 2012; 11: 4361-4372.
  • 19
    Li S, Liu H, Jin Y, Lin S, Cai Z, Jiang Y. Metabolomics study of alcohol-induced liver injury and hepatocellular carcinoma xenografts in mice. J Chromatogr B Analyt Technol Biomed Life Sci 2011; 879: 2369-2375.
  • 20
    Li ZF, Wang J, Huang C, Zhang S, Yang J, Jiang A, et al. Gas chromatography/time-of-flight mass spectrometry-based metabonomics of hepatocarcinoma in rats with lung metastasis: elucidation of the metabolic characteristics of hepatocarcinoma at formation and metastasis. Rapid Commun Mass Spectrom 2010; 24: 2765-2775.
  • 21
    Wang J, Zhang S, Li Z, Yang J, Huang C, Liang R, et al. (1)H-NMR-based metabolomics of tumor tissue for the metabolic characterization of rat hepatocellular carcinoma formation and metastasis. Tumour Biol 2011; 32: 223-231.
  • 22
    Yang Y, Li C, Nie X, Feng X, Chen W, Yue Y, et al. Metabonomic studies of human hepatocellular carcinoma using high-resolution magic-angle spinning 1H NMR spectroscopy in conjunction with multivariate data analysis. J Proteome Res 2007; 6: 2605-2614.
  • 23
    Boyault S, Rickman DS, de Reynies A, Balabaud C, Rebouissou S, Jeannot E, et al. Transcriptome classification of HCC is related to gene alterations and to new therapeutic targets. HEPATOLOGY 2007; 45: 42-52.
  • 24
    Guichard C, Amaddeo G, Imbeaud S, Ladeiro Y, Pelletier L, Maad IB, et al. Integrated analysis of somatic mutations and focal copy-number changes identifies key genes and pathways in hepatocellular carcinoma. Nat Genet 2012; 44: 694-698.
  • 25
    Laurent-Puig P, Legoix P, Bluteau O, Belghiti J, Franco D, Binot F, et al. Genetic alterations associated with hepatocellular carcinomas define distinct pathways of hepatocarcinogenesis. Gastroenterology 2001; 120: 1763-1773.
  • 26
    Folch J, Lees M, Sloane Stanley GH. A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem 1957; 226: 497-509.
  • 27
    Lanz C, Ledermann M, Slavik J, Idle JR. The production and composition of rat sebum is unaffected by 3 Gy gamma radiation. Int J Radiat Biol 2011; 87: 360-371.
  • 28
    Lanz C, Patterson AD, Slavik J, Krausz KW, Ledermann M, Gonzalez FJ, et al. Radiation metabolomics. 3. Biomarker discovery in the urine of gamma-irradiated rats using a simplified metabolomics protocol of gas chromatography-mass spectrometry combined with random forests machine learning algorithm. Radiat Res 2009; 172: 198-212.
  • 29
    Fahrner R, Beyoglu D, Beldi G, Idle JR. Metabolomic markers for intestinal ischemia in a mouse model. J Surg Res 2012; 178: 879-887.
  • 30
    Brenner RR. The oxidative desaturation of unsaturated fatty acids in animals. Mol Cell Biochem 1974; 3: 41-52.
  • 31
    Wu T. Cyclooxygenase-2 in hepatocellular carcinoma. Cancer Treat Rev 2006; 32: 28-44.
  • 32
    Gatenby RA, Gillies RJ. Why do cancers have high aerobic glycolysis? Nat Rev Cancer 2004; 4: 891-899.
  • 33
    Darpolor MM, Yen YF, Chua MS, Xing L, Clarke-Katzenberg RH, Shi W, et al. In vivo MRSI of hyperpolarized [1-(13)C]pyruvate metabolism in rat hepatocellular carcinoma. NMR Biomed 2011; 24: 506-513.
  • 34
    Nelson DL, Cox MM. Lehninger. Principles of Biochemistry. 5th ed. New York: W.H. Freeman; 2008.
  • 35
    Cairns RA, Harris IS, Mak TW. Regulation of cancer cell metabolism. Nat Rev Cancer 2011; 11: 85-95.
  • 36
    Koppenol WH, Bounds PL, Dang CV. Otto Warburg's contributions to current concepts of cancer metabolism. Nat Rev Cancer 2011; 11: 325-337.
  • 37
    Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 2009; 324: 1029-1033.
  • 38
    Lee SY, Jeon HM, Ju MK, Kim CH, Yoon G, Han SI, et al. Wnt/Snail signaling regulates cytochrome C oxidase and glucose metabolism. Cancer Res 2012; 72: 3607-3617.
  • 39
    Chafey P, Finzi L, Boisgard R, Cauzac M, Clary G, Broussard C, et al. Proteomic analysis of beta-catenin activation in mouse liver by DIGE analysis identifies glucose metabolism as a new target of the Wnt pathway. Proteomics 2009; 9: 3889-3900.
  • 40
    Wang B, Hsu SH, Frankel W, Ghoshal K, Jacob ST. Stat3-mediated activation of microRNA-23a suppresses gluconeogenesis in hepatocellular carcinoma by down-regulating glucose-6-phosphatase and peroxisome proliferator-activated receptor gamma, coactivator 1 alpha. HEPATOLOGY 2012; 56: 186-197.
  • 41
    Lambrecht M, Haustermans K. Clinical evidence on PET-CT for radiation therapy planning in gastro-intestinal tumors. Radiother Oncol 2010; 96: 339-346.
  • 42
    Chan IS, Guy CD, Chen Y, Lu J, Swiderska M, Michelotti GA, et al. Paracrine Hedgehog signaling drives metabolic changes in hepatocellular carcinoma. Cancer Res 2012; 72: 6344-6350.
  • 43
    Finlay DK. Regulation of glucose metabolism in T cells: new insight into the role of phosphoinositide 3-kinases. Front Immunol 2012; 3: 247.
  • 44
    Foster R, Griffin S, Grooby S, Feltell R, Christopherson C, Chang M, et al. Multiple metabolic alterations exist in mutant pi3k cancers, but only glucose is essential as a nutrient source. PLoS One 2012; 7: e45061.
  • 45
    Beckonert O, Monnerjahn J, Bonk U, Leibfritz D. Visualizing metabolic changes in breast-cancer tissue using 1H-NMR spectroscopy and self-organizing maps. NMR Biomed 2003; 16: 1-11.
  • 46
    Skill NJ, Scott RE, Wu J, Maluccio MA. Hepatocellular carcinoma associated lipid metabolism reprogramming. J Surg Res 2011; 169: 51-56.
  • 47
    Saito S, Ojima H, Ichikawa H, Hirohashi S, Kondo T. Molecular background of alpha-fetoprotein in liver cancer cells as revealed by global RNA expression analysis. Cancer Sci 2008; 99: 2402-2409.
  • 48
    Budhu A, Roessler S, Zhao X, Yu Z, Forgues M, Ji J, et al. Integrated metabolite and gene expression profiles identify lipid biomarkers associated with progression of hepatocellular carcinoma and patient outcomes. Gastroenterology 2013 [Epub ahead of print].