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Fig. 5 | Journal of Experimental & Clinical Cancer Research

Fig. 5

From: Breast cancer patient-derived microtumors resemble tumor heterogeneity and enable protein-based stratification and functional validation of individualized drug treatment

Fig. 5

DigiWest-based protein pathway profiling of BC-PDMs. Hierarchical cluster linkage analysis (HCL) of median-centered, log2 transformed AFI protein signals of n = 42 BC-PDMs, divided into cell cycle, MAPK/RTK and PI3K/Akt pathways. Molecular subtype classifications of BC-PDMs as indicated. (A) HCL of sample and cell cycle-related analytes with complete linkage. Four sample clusters were identified based on differential expression levels. (B) HCL of sample and MAPK/RTK-related analytes with average linkage. There are two main sample clusters (excl. BC-PDM #25) that separate samples with high MAPK/PI3K protein expression from those with low expression. (C) HCL of sample and PI3K/AKT-related analytes with complete linkage. Two main sample clusters were identified: “high-expression” and “low-expression”. (D) Differences in signal transduction in BC-PDMs samples. Box-whisker plots show median-centered, log2 transformed AFI protein signals of different pathways. Data distribution within samples is illustrated by lines connecting min. and max. values. Each red dot represents a protein. Black lines in box plots indicate the “median” of measured proteins within a sample. Blue lines delineate the values >|1| corresponding to a fold change > 0.5. (E) TNBC BC-PDMs showing elevated PI3K/AKT- and MAPK/RTK- pathway activity. The averaged, log2 transformed protein signals are compared between TNBC and HR+ BC-PDMs within different pathways. Mann–Whitney U test, PI3K: p = 0.006, MAPK/RTK: p = 0.032. (F) Differentially expressed proteins in TNBC BC-PDMs. Comparison of mean protein expression in TNBC vs. HR+ BC-PDMs. Enhanced protein abundances in TNBC BC-PDMs were found for several proteins associated with cell cycle, metabolism, immune system, PI3K/AKT, MAPK/RTK and NFkB pathway. Mann–Whitney U test, *p < 0.05, **p < 0.01, ***p < 0.001. Data are mean with SEM

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