A single-cell atlas of bladder cancer unveils dynamic cellular composition and endothelial functional shifts during progression

作者：Hongjian Song, Guoxi Xie, Yaowei Li, Xiaowei Hu, Zongzheng Yang, Yubo Zhao, Qing Shi, Haonan Li, Ziyi Liu, Zhihao Yin, Ziqi Wang, Zhichao Tong, Wanhai Xu · 发表于：Discover Oncology · 年份：2025 · DOI：10.1007/s12672-025-02297-6 · 被引用次数：8 · 研究领域：Single-cell and spatial transcriptomics、Ferroptosis and cancer prognosis、Bladder and Urothelial Cancer Treatments

Bladder cancer (BC) is characterized by high heterogeneity, with non-muscle-invasive (NMIBC) and muscle-invasive (MIBC) stages differing significantly in clinical behavior and outcomes. The transition from NMIBC to MIBC involves extensive tumor microenvironment (TME) remodeling, particularly in endothelial cells (ECs), which drive angiogenesis and modulate immune and extracellular matrix (ECM) interactions. However, the precise roles of ECs in this progression remain poorly defined. Public single-cell RNA sequencing (scRNA-seq) datasets from 47 BC patients were analyzed to characterize endothelial cell heterogeneity and functional states across NMIBC and MIBC. Computational tools such as CellChat were applied to reconstruct cell–cell communication networks, focusing on pathways related to angiogenesis, immune crosstalk, and ECM remodeling. Twelve major cell types were identified, with endothelial cells exhibiting distinct transcriptional profiles between NMIBC and MIBC. NMIBC-associated ECs promoted adhesion and migration through HMGB1 and CXCL12 signaling. In contrast, MIBC was enriched in an ADAM10 + endothelial subset associated with vascular remodeling and activation of Wnt signaling via CTNNB1. Key ligand-receptor interactions highlighted the dynamic roles of ECs in TME modulation during BC progression. This study reveals stage-specific endothelial cell phenotypes and signaling networks in BC. The identification of an MIBC-specific ADAM10 + endothelial subset underscores...