Fig. 3

Development and validation of THR-70. A Heatmap showing the expression of the three hormone receptors ER, AR, and VDR across the different triple hormone receptor (THR) groups (top). The Pie charts (bottom) show the percentages of PAM-50 subtypes in the different THR groups in the BC855 cohort. B Venn diagram showing the genes in common between the top differentially expressed genes (DEGs) between the THR-0/1 and THR-2/3 groups in the CCLE and BC855 cohorts, using p < 0.05 as a cut-off. The THR-70 signature comprises the top 70 DEGs in common between both cohorts based on SAM-fold expression. C Heatmap of the expression of THR-70 genes in normal breast epithelial clusters reported in Bhat-Nakshatri et al. Expression levels are z-score transformed. D Violin plots comparing the enrichment of THR-70 across normal breast epithelial clusters identified by Kumar et al. Signature scores (normalized U statistics between 0 and 1), shown on the Y axis, were computed using UCell. E–F Kaplan–Meier survival plots in the METABRIC cohort comparing the overall survival (OS) between patients predicted as low (Q1) and high-risk (Q4) by THR-70. The high-risk samples have significantly worse OS compared to low-risk samples in the PAM-50 basal (HR = 2.2, 95%CI: 1.2–4.1, p = 0.01), Claudin-low (HR = 6.6, 95%CI: 2.5–17.2), Luminal A (HR = 2.9, 95%CI: 2.1–4.0, p < 0.0001), and Luminal B (HR = 4.2, 95%CI: 2.5–6.9, p < 0.0001) (E). Additionally, in clinical 3-gene classifier ER-/HER2- (HR = 2.7, 95%CI: 1.6–4.5, p < 0.0001), ER + /HER2- high proliferation (HR = 4.8, 95%CI: 2.9–8.0, p < 0.0001), and ER + /HER2- low proliferation (HR = 2.9, 95%CI: 2.1–4.1, p < 0.0001) (F). Survival time is in months. Hazard ratios (HR) and 95% confidence intervals (CI) are shown. Statistically significant HRs are highlighted in red