ArticleDiscover oncology2026
A machine learning-guided epithelial plasticity score refines prognostication and immune-context stratification in muscle-invasive bladder cancer.
Article in Discover oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
purposeMuscle-invasive bladder cancer (MIBC) remains biologically heterogeneous, and clinicopathological variables do not fully capture epithelial-state remodeling linked to progression and treatment response. We developed an epithelial plasticity-related risk score (EPRS) and evaluated its prognostic, biological, and immunological relevance.
methodsUsing 368 primary TCGA-MIBC cases, we built a basal-luminal plasticity axis and integrated differential expression, correlation with the continuous plasticity index, and survival association to define 331 candidate genes. Consensus clustering, weighted gene co-expression network analysis, and 10 modeling strategies were used for subtype discovery and score development. EPRS was externally validated in GSE32894 and GSE13507 and further characterized by enrichment analysis, immune deconvolution, single-cell RNA sequencing, immunotherapy-related analyses, and nomogram construction.
resultsTwo stable plasticity-associated subtypes showed distinct overall survival. WGCNA identified opposing lipid-metabolic and extracellular-matrix/injury-response programs. Among portable models, the Ridge-based EPRS showed the most stable cross-cohort performance and significantly stratified survival in TCGA-MIBC, GSE32894, GSE13507, and the pooled meta cohort. High-EPRS tumors were enriched for extracellular-matrix remodeling, inflammatory signaling, stromal expansion, and an immune-evasive microenvironment despite increased checkpoint-related expression. Single-cell analysis linked EPRS to a continuous malignant epithelial-state landscape. An EPRS-based nomogram improved individualized survival estimation.
conclusionsEPRS captures a clinically relevant epithelial plasticity axis in MIBC and links poor outcome to stromal-immune remodeling and malignant epithelial-state organization.
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