Fig. 8.

Spatial mapping of molecular gene signatures reveals MBGS-hot tumors are immune excluded.

(A) Representative H&E and spatial gene expression plots of Boyault molecular subclassification and mutated-β-catenin gene signature (MBGS) on same tissue section for a MBGS-hot and MBGS-low tumor. MBGS overlaps with Boyault G5/G6 but is exclusive to Boyault G1/G2 tumors. (B) Representative H&E and spatial gene expression plots of Lachenmayer Wnt signatures and MBGS on same tissue section. Spatial mapping of MBGS highlights tumor nodules more clearly than previously published Wnt-CTNNB1 signatures. (C) Representative H&E and spatial gene expression plots of Sia immune signatures and MBGS on same tissue section. MBGS-hot tumors are immune excluded inside tumor nodules but may have an inflamed stroma. For (A–C), relative expression module scores are depicted with red being higher expression and blue being lower expression. (D) Diagnostic and therapeutic proposed work-up algorithm using MBGS as a companion diagnostic. Patients which are MBGS-high may benefit from anti-β-catenin therapies + ICIs. Figure created using BioRender.com.