Fig. 6: Claudin-low subgroups jointly display high EMT features and MAPK pathway activation.

a, c, e ssGSEA score distribution for each molecular subtype, from METABRIC and TCGA cohorts, related to a EMT, c TP53, and e RAS/MAPK pathways. d TP53 somatic mutation distribution across breast molecular subtypes of METABRIC and TCGA cohorts. b, f Protein-based pathway scores (RPPA data) for each molecular subtype from TCGA breast tumors related to b EMT and f RAS/MAPK. g Principal component analysis (PCA) of TCGA breast tumors according to EMT, RAS/MAPK, cell cycle/proliferation, hormone-related and DDR pathways at RNA (ssGSEA scores), and protein (RPPA scores) levels. For each sample, molecular subtype is indicated in color and variables (pathways) are highlighted in black squares. h IC50 distribution according to molecular subtype for three different MEK inhibitors available in the GDSC database. Claudin-low cell lines commonly exhibit higher sensitivity to MAPK inhibitors than other breast molecular subgroups. Wilcoxon tests. Boxplot: center line, median; box limits, upper and lower quartiles; whiskers, minimum to maximum; all data points are shown. TP53 signaling pathway signature: GO positive regulation of signal transduction by p53 class mediator; MAPK signaling signature: KEGG MAPK signaling pathway. DDR: DNA damage response; EMT: epithelial-mesenchymal transition; RPPA: reverse-phase protein array.