Fig. 2

Hh-activated stroma defines a novel transcriptional signature robustly associated with poor-prognosis in TNBC. a Expression of genes significantly downregulated (blue) or upregulated (red) (cut-off log₂ (Fold Change) ≥ 2; vertical lines) in the stroma of M6-Hh tumors compared to the stroma of M6-Ctrl or M6-Hh tumors treated with SMOi (100 mg/kg/bid), plotted against FDR values (horizontal lines indicate −log¹⁰ (FDR) > 2). Each symbol represents the transcriptome of the stromal population from five biological replicates per treatment group. b RNA-Seq analysis reveals significant enrichment of GO groups related to ECM organization and production in M6-Hh tumor stroma (FDR q value < 0.05). c Heat maps demonstrating relative expression levels of gene-sets defined by RNA-Seq analysis. Genes highlighted in red represent those that are directly involved in ECM production. Data show normalized row Z-score (n = 5 biological replicates for each treatment group). d Kaplan−Meier curves of overall survival in unstratified breast cancer patients and in patients with basal, TNBC. Blue and red lines represent low and high Hh-stromal gene signature expression (HSGS), respectively. Statistical significance was determined using the Log-rank test; ***P < 0.001