Fig. 5: Patient-derived organoids (PDO) of multiple PCa cases preserve molecular signatures of the matched tissue and can be used to determine drug sensitivity in vitro.
From: Patient-derived xenografts and organoids model therapy response in prostate cancer
a Representative brightfield images of PDOs from PCa (“tumor”) and from cancer unaffected control area (“benign”) from the same patient (scale bar 100 μm). Representative images of PDOs with an acinar or cystic morphology and with an adenocarcinoma-like morphology (“acinar” (scale bar 500 μm) and “adenocarcinoma” (scale bar 50 μm), respectively). b. Overview of the genetic profiles of N = 11 PCa tissue samples and matching PDOs, determined by targeted sequencing of PCa-specific mutation panels. c Binary heatmap plot of the data presented in b. Rows represent samples (tissue (T) and organoids (O) for each case), columns represent genomic mutations. d Correlation plots of gene expression between tissue and matched organoids for PCa case 61 (left) and case 62 (right). Pearson correlation coefficient, r: 0.795 and 0.858, respectively. For both correlations, p value < 2.2e10−16. e Results of PDO drug screen assay on three advanced PCa cases (P80, P82, P89) and two primary PCa cases (P133 and P134). Normalized viability z scores are shown in the heatmap, with unsupervised hierarchical cluster analysis of the drugs. Asterisks indicate a significant reduction of viability compared to vehicle (*p < 0.05). Statistical significance was determined by two-tailed t-test for abiraterone (vehicle EtOH) and by one-way ANOVA with Dunnett correction for all remaining drugs (vehicle DMSO). Non-determined values are indicated in gray squares. Drug targets are indicated in the legend and reported by a colored-coded square below each drug.
