Methylation Profiles Reveal Distinct Subgroup of Hepatocellular Carcinoma Patients with Poor Prognosis
Figure 4
Integrated analysis of methylation and gene expression in 59 HCC patients.
(A) Hierarchical clustering of the 3185 most significantly differentially expressed genes between tumors and adjacent non-tumorous tissues. (B) Starburst plot was constructed by plotting transformed log10 p-value of differentially expressed genes (Y-axis) versus transformed log10 p-value of methylation difference (X-axis) between tumor and adjacent non-tumorous tissues. Genes with FDR adjusted p-value<0.05 were labeled in black. Genes with absolute fold change >1.2, difference in β-value greater than 0.1 and which met the statistical cut-off (FDR adjusted p-value<0.05) were labeled in red. Directional change of expression and methylation are indicated by the black arrow head. Table at lower panel shows the percentage of genes with significant positive and negative correlations between gene expression and methylation data. (C) Validation results for SH3YL1, CYB5R2, SPINT2 and GSTP1. Methylation and gene expression data were validated by pyrosequencing and quantitative PCR respectively. T-test was used to compare the difference in methylation or gene expression between two groups; Pearson correlation was used to measure association between pyrosequencing and Infinium data, and between gene expression and methylation data. (D) Top network derived from the 536 aberrantly methylated and deregulated genes where NFκB complex served as primary node. (E) Predicted upstream regulators from IPA. Eleven upstream regulators (including NFκB complex) were associated with the NFκB pathway. Red spheres indicate genes that were upregulated in tumor; green spheres indicate downregulated genes in tumor compared to adjacent non-tumorous tissues; grey boxes represent complexes and white spheres represent upstream regulators.