Gene Network Analysis of Glucose Linked Signaling Pathways and Their Role in Human Hepatocellular Carcinoma Cell Growth and Survival in HuH7 and HepG2 Cell Lines

Figure 4

Gene sets representative of normal liver and dysregulated in hepatocellular carcinoma (HCC). Sets of genes detected in either HuH7 or HepG2 cells, specifically expressed in liver or dysregulated in HCC, or regulated by glucose, have been raised from the analysis of published datasets listed in Table 1. (a) Each set is represented by gene number and percentile of crossing set; for example, among the 129 genes regulated by glucose and detected in HepG2 cells (i.e., 0.6%), 22 belong to the liver phenotype set (i.e., 17% of them) and 7 are also dysregulated in HCC (i.e., 5.4% of them). (b) Frequency of genes regulated by high (4,5 g/L) versus low (1 g/L) glucose. Asterix represents significant overrepresentativity of genes regulated by glucose. (c) Gene sets differentially expressed in HepG2 versus HuH7 cells, that is, 34 genes upregulated in HepG2 and 179 in HuH7 cell lines and representativity of liver and HCC genes in both sets. (d) Analysis of unique gene ontology (GO) biological process (left panel), cellular component (central panel), and molecular function (right panel) significantly overrepresented in the set of genes dysregulated in HepG2 versus HuH7 cell line. The set of genes dysregulated in HepG2 versus HuH7 (213 genes) was compared to sets of genes representing liver phenotype (4918 genes) or those dysregulated in hepatocellular carcinoma (806 genes) using FatiGO+ software (http://babelomics.bioinfo.cipf.es/).

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