2026/05/13 by Kai Yu, Jianfeng Chen, Yu-Yi Chu +49 · 1 voice
Biochemistry, Genetics and Molecular Biology · Medicine · #Bladder and Urothelial Cancer Treatments #Cancer Immunotherapy and Biomarkers #Single-cell and spatial transcriptomics
paper · doi:10.1158/2159-8290.cd-26-0099
openalex publication_date 2026/05/13 · openalex created_date 2026/05/14 · openalex updated_date 2026/07/30
Muscle-invasive bladder cancer (MIBC) is clinically heterogeneous, and current molecular subtyping does not capture the spatial organization of tumor states and microenvironmental context. Here, we construct a spatial atlas of MIBC by integrating spatial transcriptomics from 22 tumors with matched bulk RNA and whole-exome sequencing data. We identify a continuous, spatially organized luminal-to-basal axis within individual tumors that is associated with greater chromosomal instability and transcriptional plasticity. Luminal tumor cores are enriched for FGFR3 and NECTIN4, whereas basal-like states localize toward invasive margins and are associated with elevated EGFR signaling, epithelial-mesenchymal transition, genomic instability, immune infiltration, and greater chemotherapy sensitivity. Spatial analyses further reveal lineage- and location-associated differences in tertiary lymphoid structure states. Pan-cohort analyses across over 3,000 tumors confirm conserved FGFR3-EGFR lineage exclusivity and associated immune programs. Together, these findings define a spatial framework for understanding lineage states, immune architecture, and therapeutic vulnerabilities in MIBC.