ICR score correlated negatively with certain cancer-cell pathways in all CMS subtypes (for example, WNT-β catenin and NOTCH signaling), whereas a positive correlation with immunosuppressive and stromal-related pathways (for example, transforming growth factor (TGF)-β, epithelial to mesenchymal transition and vascular endothelial growth factor signaling) was only observed in CMS4 tumors (Extended Data Fig. 2f). The gene discussed is VEGFA; the disease is cancer.