ArticleClinical and translational medicine2026
SPP1-driven spatial niche remodelling defines aggressive progression in the basal subtype of upper tract urothelial carcinoma.
Article in Clinical and translational medicine, 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
backgroundUpper tract urothelial carcinoma (UTUC) is a rare, aggressive malignancy representing 5%‒10% of urothelial carcinomas. Its basal subtype remains understudied but is preferentially associated with muscle invasion and poorer disease-specific survival (DSS). Although the genomic landscape of UTUC has been extensively profiled, current bulk transcriptomic classification cannot resolve cellular heterogeneity or spatial organisation, potentially obscuring subtype-specific microenvironmental programs.
methodsWe integrated single-cell RNA sequencing and spatial transcriptomics to resolve relationships among molecular subtype, muscle invasion and cellular heterogeneity within the UTUC microenvironment. Cellular communication and multiscale spatial analyses identified spatial programs, with tissue-level validation by multiplex immunofluorescence. These programs were further examined in external bladder cancer datasets spanning single-cell, spatial and GeoMx platforms. SPP1 knockdown in J82 cells tested epithelial-intrinsic effects. We evaluated the subtype-discriminatory and prognostic relevance of SPP1 in the Japan-UTUC cohort.
resultsBasal UTUC exhibited an immune‒stromal-enriched microenvironment primarily associated with molecular subtype rather than pathological stage. Within basal tumours, muscle invasion coincided with increased heterogeneity and two spatial programs. A conserved SPP1
conclusionsBasal UTUC has a largely stage-independent, immune‒stromal-enriched background that is spatially reorganised with muscle invasion, with an SPP1-associated myeloid‒stromal boundary program as its most reproducible feature. Spatial, functional and clinical evidence supports the prognostic value of SPP1 and warrants its evaluation as a therapeutic target.
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