Figure 3

Integrative analysis of microarray-based comparative genomic hybridization, gene expression and Ki67-based response data. (A) Matched heatmaps of gene expression and aCGH within two amplified loci; 11q13.2-q13.4 and 17q12-q21.1. Bar plots show the result of a Mann-Whitney U-test for expression as a continuous variable and gene amplification as the grouping variable. Bars in red show adjusted P-values <0.05. aCGH, green copy number loss; black, no copy number change; dark red, copy number gain; bright red, gene amplification; gene expression: green, downregulation; red, upregulation; MWU, Mann-Whitney U-test; adjp, adjusted P-value. (B) Venn diagram shows the intersect between the list of genes that are overexpressed when amplified and those genes that are associated with a poor response to AI when amplified. The call-out box lists these genes and their loci, highlighting that only three genes are upregulated in long-term estrogen deprived (LTEDs). (C) Scatter plots demonstrating that for each of the three genes selected for functional validation, significant negative correlation was identified between the aCGH-derived cbs ratios and the percentage decrease in Ki67 following 2 weeks of AI therapy. In each plot, cbs-smoothed ratios are plotted on the y-axis while the percentage decrease in Ki67 at 2 weeks is plotted on the x-axis. Red, CHKA, Blue, LRP5, Green, SAPS3.