Metabolomics offers the opportunity to characterize complex diseases like hepatocellular carcinoma (HCC) through a systematic evaluation of thousands of metabolites in human liver tissues and fluids. In this study, we compared the metabolomic profiles of HCC and cirrhotic patients before and after liver transplant. This was accomplished by untargeted analysis of plasma samples using gas chromatography coupled with mass spectrometry (GC-MS). Plasma samples from 12 patients (6 HCC cases and 6 patients with liver cirrhosis) were collected before and after transplant. The participants were frequency-matched by physiological variables. After protein depletion, metabolites were extracted from the plasma samples. The metabolite extracts were then derivatized before GC-MS data acquisition. The raw GC-MS data were preprocessed by performing outlier screening, peak detection and deconvolution, retention index calibration, alignment, and metabolite identification by NIST and Fiehn library search. A total of 736 analytes have been detected for further statistical analysis. A repeated measures ANOVA model with mixed effects was used to evaluate multiple comparisons among and within HCC and cirrhotic groups. 43 metabolites were selected as statistically significant with adjusted p-value < 0.05. Out of these, 22 metabolites have putative identifications. It was observed that the post-transplant profiles for HCC and cirrhotic patients were very similar. In a previous biomarker study conducted using plasma samples from HCC cases and cirrhotic controls prior to liver transplant, our team found significant changes in the levels of citric acid, L-glutamic acid, L-Tyrosine, L-Threonine, L-Phenylalanine, L-leucine, and D-Fructose. Interestingly, in the present study, we observed that these metabolites have changed significantly after transplant. A pathway analysis using Ingenuity Pathway Analysis tool revealed that tRNA charging pathway is enriched in both HCC and cirrhotic patients, after transplant.

CITATION INFORMATION: Desai C, Varghese R, Robertazzi S, Di Poto C, Ferrarini A, Tu C, Girlanda R, Khan K, Fishbein T, Ressom H. Metabolomic Profiles of Hepatocellular Carcinoma and Cirrhotic Patients Before and After Transplantation. Am J Transplant. 2016;16 (suppl 3).

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