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

Hepatocarcinoma (HCC) has a very high mortality rate and the high recurrence and metastasis rates contribute to the poor prognosis of HCC patients. To understand HCC formation and metastasis, we assessed the metabonomics of rat HCC and HCC with lung metastasis (HLM). The HLM rat model was established by exposure to diethylnitrosamine (DEN). Levels of serum and urine metabolites were quantified with gas chromatography/time-of-flight mass spectrometry (GC/TOFMS), and data were analyzed with partial least-squares discrimination analysis (PLS-DA). Serum and urine levels of some metabolites differed significantly between the control, HCC, and HLM groups. The products and intermediates from glycolysis and glutamate metabolism were elevated, while the tricarboxylic acid (TCA) cycle was inhibited, in both HCC and HLM. HLM samples revealed enhanced metabolism of nucleic acids, amino acids and glucuronic acid. PLS-DA indicated that principal component weighting was greatest for serum serine, phenylalanine, lactic acid, tyrosine and glucuronic acid, and urine glycine, serine, 5-oxyproline, malate, hippuric acid and uric acid. These data provide novel information that will improve understanding of the pathophysiological processes involved in HCC and HLM, and revealed potential metabolic markers for HCC invasion and metastasis. Copyright (c) 2010 John Wiley & Sons, Ltd.