Fig. 1.

14-3-3τ is up-regulated in breast cancer, and its up-regulation is significantly associated with decreased ERα66 expression, tamoxifen resistance, and relapse-free survival. (A) 14-3-3τ expression is significantly elevated in 14 cancers from TCGA database compared with normal tissue expression. Tumor samples are denoted with bolded lines. Significance calculated by Mann-Whitney U test. AC, adenocarcinoma; SC, squamous cell carcinoma; PA, papillary cell carcinoma. (B) 14-3-3τ expression is significantly (P = 7.95e-4) increased in breast cancer compared with their matched, normal breast tissues in the TCGA BRCA dataset. (C) 14-3-3τ is overexpressed in about 60% of breast tumors when compared with their matched, adjacent normal breast tissues in three cohorts: TCGA, Wang et al. (22) and Li et al. (21). 14-3-3τ overexpression in Wang et al. is defined by ≥ 1.5X of their matched normal breast tissues on Western blot analysis. The cutoff for TCGA and Li et al. is the 14-3-3τ expression level in the respective matched normal breast tissues. IHC, immunohistochemistry. (D) 14-3-3τ expression significantly increases from luminal A and luminal B to basal-like breast cancer subtype (P = 3.00e-53 and P = 2.9e-25, respectively). (E) METABRIC relapse-free survival analysis showing breast cancer patients with high 14-3-3τ expression (red) are significantly (P = 3.63e-4) more likely to relapse than patients with low expression (blue). Patients were split by upper tertile of 14-3-3τ expression in their breast cancers. Similar results were obtained when patients were split by upper quartile or median. (F) High 14-3-3τ expression is significantly (P = 2.89e-19) associated with low ERα66 protein expression in breast cancer RPPA analysis of TCGA BRCA samples. Cutoff was defined by 14-3-3τ expression Z score >1. Similar results were obtained when using other cut-offs. (G) ER+ patients with high 14-3-3τ expression are significantly (P = 7.7e-05) less likely to respond to TAM treatment (TCGA). (H) ER+ patients treated with TAM who have high 14-3-3τ expression (red) are significantly (P = 0.007) more likely to relapse than patients with low 14-3-3τ expression (black) (Loi cohort (28)). (I) High 14-3-3τ expression (red) only significantly impacts relapse-free survival in ER+ patients compared with ER– patients breast cancer (METABRIC). Patients were split by upper tertile of 14-3-3τ expression in their breast cancers. HER2, human epidermal growth factor receptor 2; HR, hazard ratio; RNA-seq, RNA sequencing.