Journal: Clinical Cancer Research
Article Title: Tamoxifen Response at Single-Cell Resolution in Estrogen Receptor–Positive Primary Human Breast Tumors
doi: 10.1158/1078-0432.CCR-23-1248
Figure Lengend Snippet: Identification and characterization of resistant tumor cell subpopulations in four tamoxifen-responsive tumor pairs. A, Individual cells were assigned a score from the T47D tamoxifen response signature compared with cluster matched untreated score. Application of response score to UMAP plot demonstrated three distinct clusters with enriched signature score on treatment (cluster 3, 12, 19) and one tamoxifen-sensitive cluster with depletion of response score (cluster 2). B, Abundance of cells from resistant clusters in each of the four tumors. C, Stacked bar chart showing distribution of cells within 22 distinct clusters, color coded by tumor and treatment condition. D, Kaplan–Meier (KM) curve of the cluster 19 signature (scTAM-resistance-C19), using ER + /HER2 − patients that received endocrine therapy from METABRIC. Higher signature score predicted worse overall survival (HR, 2.17; P < 0.001). Survival curve differences were calculated by the log-rank test and the estimates of survival probabilities and cumulative hazard with a univariate Cox proportional hazards model. E, We obtained data of clinically annotated endocrine therapy sensitive and resistant tumors from Xia and colleagues . All three tamoxifen resistance signatures were enriched in resistant tumors compared with sensitive. Significance was determined using the Wilcoxon rank-sum test, ***, P < 0.001.
Article Snippet: We obtained the ER + /HER2 − cell line T47D from the ATCC.
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