A classification based on tumor-stroma ratio and tumor budding for patients with muscle-invasive bladder cancer

Background Tumor-stroma ratio (TSR) and tumor budding (TB) play important roles in muscle-invasive bladder cancer (MIBC). We developed a rating system (TSR-TB type) based on the morphological evaluation of TSR and TB for predicting patient outcome and using individualized care. Methods TSR and TB were assessed in publicly accessible MIBC tumor slides from the TCGA database. MIBC patients were classified as low stromal or high stromal type based on TSR, and high stromal type was further classified as compartmentalized or mixed stromal type based on TB. Results TSR-TB type was an independent adverse prognostic factor for OS (P < 0.001). Low stromal type had a greater prognosis (P < 0.001) and were enriched for FGFR3 mutations (P = 0.001). The mixed stromal type was distinguished by increased M2 macrophage penetration (P < 0.001), anti-tumor immune activity, DNA repair pathway mutations, and poor survival. GSEA showed that certain cancer-related pathways, such as mitotic spindle, PI3K-AKT-MTOR signalingwere hyperactivated in high stromal type (all FDR<0.05). Furthermore, mixed stromal type demonstrated enhanced activation of epithelial mesenchymal transformation (EMT), inflammatory response (all FDR<0.05). Conclusion TSR and TB-based MIBC classification coincides with patient survival and molecular alterations. The identified subtypes may have important implications for individualized MIBC therapy.