Prognostic Significance of Lineage Diversity in Bladder Cancer Revealed by Single-Cell Sequencing

Bladder cancer is the most common malignant tumor of the urinary system. We investigated the clinical implications of cell lineages in bladder cancer by integrating single-cell and bulk transcriptome data. By investigating the single-cell transcriptional profiles of 12,424 cells from normal bladder, eleven cell types and five types of epithelial sub-population were identified. Based on the signature of cell types identified in single-cell profiles, deconvolution analysis was employed to estimate cell types and epithelial lineages in the bulk RNA sequencing bladder cancer cohort. Cancer subtypes with clinical implications were further identified based on the heterogeneity of the epithelial lineage across patients. This study suggests that the EMT-like subtype is robustly correlated with poor prognosis and the umbrella subtype is a positive factor for the patient survival. Our research has a high potential for accurate prognostic and therapeutic stratification of bladder cancer.