LAUSR.org creates dashboard-style pages of related content for over 1.5 million academic articles. Sign Up to like articles & get recommendations!

Identification of the Consistently Altered Metabolic Targets in Human Hepatocellular Carcinoma

Photo by theyshane from unsplash

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… Click to show full abstract

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, ∼60% of which are not yet described in HCC. The down-regulated 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.

Keywords: hepatocellular carcinoma; metabolic targets; metabolic genes; consistently altered; altered metabolic; human hepatocellular

Journal Title: Cellular and Molecular Gastroenterology and Hepatology
Year Published: 2017

Link to full text (if available)


Share on Social Media:                               Sign Up to like & get
recommendations!

Related content

More Information              News              Social Media              Video              Recommended



                Click one of the above tabs to view related content.