Journal
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
Volume 4, Issue 2, Pages 303-+Publisher
ELSEVIER INC
DOI: 10.1016/j.jcmgh.2017.05.004
Keywords
Liver Cancer; HCC; Tumor Metabolism
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Funding
- Niger, Delta Development Commission, Nigeria
- Graduate School (HBIGS), University of Heidelberg, Germany
- Deutsche Forschungsgemeinschaft (DFG) [Me4532/1-1]
- DFG [Do373/13-1]
- BMBF program LiSyM [PTJ-FKZ: 031 L0043]
- Marie Curie Actions of the European Union's Seventh Framework Programme (FP7) [PITN-GA-2012-316549]
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BACKGROUND & AIMS: Cancer cells rely on metabolic alterations to enhance proliferation and survival. Metabolic gene alterations that repeatedly occur in liver cancer are largely unknown. We aimed to identify metabolic genes that are consistently deregulated, and are of potential clinical significance in human hepatocellular carcinoma (HCC). METHODS: We studied the expression of 2,761 metabolic genes in 8 microarray datasets comprising 521 human HCC tissues. Genes exclusively up-regulated or down-regulated in 6 or more datasets were defined as consistently deregulated. The consistent genes that correlated with tumor progression markers (ECM2 and MMP9) (Pearson correlation P <.05) were used for Kaplan-Meier overall survival analysis in a patient cohort. We further compared proteomic expression of metabolic genes in 19 tumors vs adjacent normal liver tissues. RESULTS: We identified 634 consistent metabolic genes, similar to 60% of which are not yet described in HCC. The downregulated genes (n = 350) are mostly involved in physiologic hepatocyte metabolic functions (eg, xenobiotic, fatty acid, and amino acid metabolism). In contrast, among consistently up-regulated metabolic genes (n = 284) are those involved in glycolysis, pentose phosphate pathway, nucleotide biosynthesis, tricarboxylic acid cycle, oxidative phosphorylation, proton transport, membrane lipid, and glycan metabolism. Several metabolic genes (n = 434) correlated with progression markers, and of these, 201 predicted overall survival outcome in the patient cohort analyzed. Over 90% of the metabolic targets significantly altered at the protein level were similarly up-or down-regulated as in genomic profile. CONCLUSIONS: We provide the first exposition of the consistently altered metabolic genes in HCC and show that these genes are potentially relevant targets for onward studies in preclinical and clinical contexts.
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