From tissue architecture to precision oncology: spatial transcriptomics of bladder cancer

Abstrakt:

Urothelial carcinoma of the urinary bladder is a biologically heterogeneous malignancy characterized by substantial variability in its morphological and molecular features. The aim of this study was to evaluate the potential of spatial transcriptomics for identifying biologically distinct tumour populations within invasive urothelial carcinoma. Spatial transcriptomic profiling was performed on a formalin-fixed paraffin-embedded (FFPE) specimen of invasive bladder carcinoma using the 10x Genomics Visium Spatial Gene Expression platform. Transcriptomic data were analysed using cluster analysis and differential gene expression analysis. Six transcriptionally distinct clusters with a clear spatial organization were identified. Cluster 1 corresponded to superficial papillary non-invasive tumour formations, whereas Clusters 2 and 4 were localized within deeper papillary structures. Cluster 6 was localized at the invasive tumour front. Clusters 3 and 5 represented transitional populations containing stromal and inflammatory cells. Expression of EPCAM was detected in all tumour-associated clusters, confirming their epithelial origin. The superficial cluster was characterized by genes associated with epithelial differentiation, mucosal defence, and maintenance of epithelial polarity. The deeper Cluster 2 exhibited increased expression of cell-cycle and proliferation-related genes, including PCLAF, PLK1, STMN1, and E2F3. Cluster 4 was associated with metabolic and signalling pathways. The invasive Cluster 6 demonstrated increased expression of genes related to mitotic activity as well as genes involved in immune processes. This pilot analysis confirmed marked transcriptional heterogeneity among individual tumour compartments. The findings demonstrate the potential of spatial transcriptomics for investigating the biological diversity of urothelial carcinoma and for identifying molecular mechanisms associated with tumour progression and invasion.