Figure 3 from A Plastic EMP1+ to LGR5+ Cell State Conversion as a Bypass to KRASG12D Pharmacologic Inhibition in Metastatic Colorectal Cancer

PDAC and keratinization gene programs induced by KRAS activating mutations. A, Dot plot illustrating the scaled and normalized expression of selected marker genes across the different metastasis cell clusters (Louvain clustering, resolution = 0.6, SCT values). B, UMAP visualization showing PDAC basal cells (B) and epidermal keratinization (C) with black indicating the top 20% (quantile 80) of cells based on feature expression (TRUE) and gray indicating the remaining cells (FALSE). D, Heatmaps of in vitro APK CTOs and AKTP MTOs treated with vehicle or RMC-9945 for 48 hours, hierarchically clustered using the Ward D2 method based on keratinization gene list. E, Representative example of hematoxylin and eosin (H&E) staining on liver metastases treated with vehicle or RMC-9945 for 11 days. Scale bar, 50 μm. F, Representative example of E-cadherin immunofluorescence on liver metastases treated with vehicle or RMC-9945. Top scale bar, 100 μm. Bottom scale bar, 20 μm. G–I, Volcano plot showing expression differences of the EpiHR signature (G), the basal pancreatic signature (H), and keratinization genes (I) between samples with and without driver mutations in individual oncogenes and tumor-suppressor genes from the COAD TCGA patient cohort (n = 520 patients). The difference of median values (x axis) versus P values (Wilcoxon rank-sum test; y axis) are shown. J, Volcano plot of differential expression of samples with and without mutations in the KRAS signaling pathway. Genes of interest are highlighted. FC, fold change.