Figure 6

Methylations patterns in the HOXA locus. (A) Genomic map of the HOXA region with UC DMRs indicated (yellow). (B) UC samples were clustered (k-means, k = 3) based on their methylation profiles across the HOXA-locus into three groups of samples (posterior-only, anterior-only, and pan-HOXA). For each sample group, the average methylation for each DMR is shown across the HOXA locus. Vertical bars denote standard deviations. (C) DMR methylation and gene expression levels across the HOXA and HOXB loci. Within the heatmaps for HOXA, the horizontal lines separate the anterior region from the posterior region (between the HOXA7 and HOXA9 promoters). The DMRs and genes are in the same order as in panel A and DNA methylation is indicated in blue (low) to red (high) and gene expression in green (low) to red (high). (D) Survival analysis of UC samples stratified into the three HOXA methylation groups. Disease-specific survival (DSS) was used as endpoint. (E, F) Coordinated changes in DMR methylation and gene expression (GEX) were visualized using starburst plots for ‘pan-HOXA’ vs. ‘posterior-only’ (E) and ‘anterior-only’ vs. ‘posterior-only’ (F). Dotted lines indicate the significance threshold FDR <0.01 (t-test).