Fig. 3: Stroma-specific variations across patients highlight distinct phenotypic groups.

a Density enrichment of myCAFs, csCAFs, and reactive stroma signatures shows overlapping expression. b Enrichment of iCAF and csCAF signatures. Red circle indicates specific clustering of iCAF cells. c Enrichment of PSC signatures representing two separate subgroups. d Gene expression heatmap using Normal and Activated signatures (250 genes) clusters patients into three interpretable groups (normal, intermediate, activated) Heatmap cell colors are shown as z-score between −3 to +3. e Overlaying of the Moffitt Normal (blue) /Activated (brown) signature scores identified two distinct localizations of the prognostic phenotypes. f Pseudobulk heatmap showing differential secretome factors in the stroma between stromal subtypes. Sample tracks at the top show percentage of subpopulations in each patient stroma. g Heatmap showing differential secretome expression in the myeloid (monocyte/macrophages) between stromal subtypes. h Differential secretome/cell-contact related gene expression in the lymphocytes (T-lymphocytes) between stromal subtypes. i Graphical summary of the interaction network of TME signaling activities upregulated in the activated stroma. Circles and crescents represent ligands and paired receptors. Up/Down arrows indicate the compartmental subpopulation balances observed. Ligands are directional and activate the compartment and subpopulation where the corresponding receptor is distinctly expressed. j Graphical interaction network of upregulated signaling within the normal subtype TME. Reference to DEG: 1Fig. 1e, 2Fig S1e, 3Fig 3f, 5Fig S2g, 6Fig S1g, 7Fig S3f, 8Fig 3g, 9Fig S1f, 10Fig 3h. Heatmap colors represented by z score expression −3 to +3. Source data are provided as a Source Data file.