Fig. 5. STAT3-related genes are up-regulated in antiestrogen resistant ALDH+ cells and are associated with worse outcomes for ER+ breast cancer patients.

a Heatmap illustrating the 28 STAT3-related genes differentially expressed in ALDH+ cells of four ER+ metastatic patient-derived cells treated with antiestrogen treatments (fold change ≥2, pairwise Rank Products). Red color represents gene up-regulation while blue shows down-regulation in ALDH+ relative to ALDH- cells. b Kaplan–Meier analysis of high versus low expression of STAT3 28-gene signature showing recurrence-free survival in ER+ breast cancer patients. The gene expression data is from published microarray datasets available in KM plotter [25]. c Expression of OSMR, CTTN, MUC1, and PBX1 genes was assessed by real-time qPCR analysis and normalized to control to calculate fold change. Metastatic patient-derived cells were treated for 72 h with SFX-01 (5 μM) or water (control). d Heatmap showing OSMR and MUC1 gene expression in patient matched dataset after 3 months treatment with letrozole relative to baseline. Heatmap is ranked from left to right using the sum of the expression of the two genes. Red indicates up-regulation and blue indicates down-regulation in treated tumors relative to baseline. All significant cut-points (p ≤ 0.05) are shown in gray. The Kaplan–Meier plot demonstrates that elevated expression of these genes is significantly associated with decreased breast cancer specific survival (BCS). Vertical bars on survival curves indicate censored cases. p value is based on a log-rank (Mantel–Cox) test.