Metabolomic Analysis of Liver Tissue from the VX2 Rabbit Model of Secondary Liver Tumors.
Purpose. The incidence of liver neoplasms is rising in USA. The purpose of this study was to determine metabolic profiles of liver tissue during early cancer development. Methods. We used the rabbit VX2 model of liver tumors (LT) and a control group consisting of sham animals implanted with Gelfoam into their livers (LG). After two weeks from implantation, liver tissue from lobes with and without tumor was obtained from experimental animals (LT+/LT-) as well as liver tissue from controls (LG+/LG-). Peaks obtained by Gas Chromatography-Mass Spectrometry were subjected to identification. 56 metabolites were identified and their profiles compared between groups using principal component analysis (PCA) and a mixed-effect two-way ANOVA model. Results. Animals recovered from surgery uneventfully. Analyses identified a metabolite profile that significantly differs in experimental conditions after controlling the False Discovery Rate (FDR). 16 metabolites concentrations differed significantly when comparing samples from (LT+/LT-) to samples from (LG+/LG-) livers. A significant difference was also shown in 20 metabolites when comparing samples from (LT+) liver lobes to samples from (LT-) liver lobes. Conclusion. Normal liver tissue harboring malignancy had a distinct metabolic signature. The role of metabolic profiles on liver biopsies for the detection of early liver cancer remains to be determined.
Departments of Surgery, Case Western Reserve University, School of Medicine and University Hospitals, Case Medical Center, 11100 Euclid Avenue, Cleveland, OH 44106, USA ; Departments of Nutrition, Case Western Reserve University, School of Medicine and University Hospitals, Case Medical Center, 11100 Euclid Avenue, Cleveland, OH 44106, USA.
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Ibarra
Center for Proteomics and Bioinformatics, Case Western Reserve University, School of Medicine and University Hospitals, Case Medical Center, Cleveland, OH 44106, USA.
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Dazard
Departments of Nutrition, Case Western Reserve University, School of Medicine and University Hospitals, Case Medical Center, 11100 Euclid Avenue, Cleveland, OH 44106, USA.
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Sandlers
Departments of Surgery, Case Western Reserve University, School of Medicine and University Hospitals, Case Medical Center, 11100 Euclid Avenue, Cleveland, OH 44106, USA.
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Rehman
Departments of Surgery, Case Western Reserve University, School of Medicine and University Hospitals, Case Medical Center, 11100 Euclid Avenue, Cleveland, OH 44106, USA.
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Abbas
Departments of Nutrition, Case Western Reserve University, School of Medicine and University Hospitals, Case Medical Center, 11100 Euclid Avenue, Cleveland, OH 44106, USA.
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Kombu
Departments of Nutrition, Case Western Reserve University, School of Medicine and University Hospitals, Case Medical Center, 11100 Euclid Avenue, Cleveland, OH 44106, USA.
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Zhang
Departments of Surgery, Case Western Reserve University, School of Medicine and University Hospitals, Case Medical Center, 11100 Euclid Avenue, Cleveland, OH 44106, USA ; Departments of Nutrition, Case Western Reserve University, School of Medicine and University Hospitals, Case Medical Center, 11100 Euclid Avenue, Cleveland, OH 44106, USA.
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Brunengraber
Departments of Surgery, Case Western Reserve University, School of Medicine and University Hospitals, Case Medical Center, 11100 Euclid Avenue, Cleveland, OH 44106, USA ; Departments of Nutrition, Case Western Reserve University, School of Medicine and University Hospitals, Case Medical Center, 11100 Euclid Avenue, Cleveland, OH 44106, USA ; Department of Surgery, Cancer Treatment Centers of America, Chicago, IL 60099, USA.
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Sanabria