Figure 4

Upregulated genes that showed promoter demethylation. (a) A starburst plot comparing gene expression with promoter methylation in G-CIMP-demethylated (C.3) vs. C.1 non-codel tumors is shown. One dot represents one gene. The q-values for gene expression and promoter methylation were calculated using a paired two-sided moderated Welch’s t-test and the Benjamini-Hochberg method. Genes were considered to be upregulated with promoter demethylation (red dots) when the fold change in gene expression was >2 and methylation difference <−0.2. (b) Methylation level of IGF2BP3 in C.3 and C.1 non-codel tumors. A map of the chromosome around IGF2BP3 and the positions of methylation array probes are shown at the top. A heatmap of the methylation level of each probe is shown (bottom). Each row represents a sample, and each vertical bar represents a probe. (c) Box plots of the IGF2BP3 promoter methylation level and gene expression comparing G-CIMP-low tumors and G-CIMP-high tumors from the TCGA study. The Wilcoxon rank-sum test was used for statistical analysis. RPKM: reads per kilobase of exon per million mapped sequence reads. (d) Methylation level of IGF2BP3 in G-CIMP-low and G-CIMP-high tumors from the TCGA study is shown, similar to b. (e) Kaplan-Meier analysis of overall survival for IGF2BP3-high and -low expression tumors among G-CIMP-high and -low tumors in TCGA data. The log-rank test was used for statistical analysis.