Emergence of an adaptive epigenetic cell state in human bladder urothelial carcinoma evolution
Y. Xiao, W. Jin, K. Qian, K. Wu, G. Wang, W. Jiang, R. Cao, L. Ju, Y. Zhao, H. Zheng, T. Liu, L. Chang, Z. Xu, T. Wang, J. Luo, L. Shan, F. Yu, X. Chen, D. Liu, H. Cao, Z. Yang, S. Li, H. Shi, Z. Guo, Y. Gong, , X. Wang
Abstract
Intratumor heterogeneity (ITH) of bladder cancer (BLCA) facilitates therapy resistance and immune evasion to affect clinical prognosis directly. However, the molecular and cellular mechanism generating ITH in BLCA remains elusive. Here we show that a TM4SF1-positive cancer subpopulation (TPCS) drives ITH diversification in BLCA. By extensive profiling of the epigenome and transcriptome of BLCA from 79 donors across all stages, we elucidated the evolution trajectories of luminal and basal BLCA. TPCS emerges from the basal trajectory and shows extensive transcriptional plasticity with a distinct epigenomic landscape. Clinically, TPCS were enriched in advanced stage patients and associated with poor prognosis. Our results showed how cancer adapts to its environment by adopting a stem cell-like epigenomic landscape.
02 /Specification & Classification
Click any tag to browse matching papersReproducibility ledger
Nobody has reported trying to reproduce this paper yet. Did you replicate an experiment or run the code? Your report saves the next lab a week.
Sign in to file a reproducibility report.
Related papers
- Intrinsic higher potency of basal urothelial cells to intermediate and umbrella cells as the cell of origin for bladder cancer
Chuan Yu, Nicholas Chu, … Zhu A. Wang·bioRxiv·Jun 28, 2025
- Epigenetic Subtypes of High-Grade T1 Bladder Cancer Reveal Intra-Tumor Heterogeneity and Distinct Interactions with Tumor Microenvironment.
Joaquim Bellmunt B, Yingtian Xie, … Paloma Cejas·TheranosticsPeer-reviewed·May 18, 2026
- Subtype-specific epigenomic landscape and 3D genome structure in bladder cancer
Tejaswi Iyyanki, Baozhen Zhang, … Feng Yue·Genome biologyPeer-reviewed·Apr 15, 2021
- Epigenomic mapping identifies a super-enhancer repertoire that regulates cell identity in bladder cancers through distinct transcription factor networks
H. Neyret-Kahn, J. Fontugne, … F. Radvanyi·bioRxiv·Jan 11, 2022
- Histologic variants in bladder cancer harbor aggressive molecular features including TM4SF1 expression and a CA125+ cell state
Heiko Yang, Hanbing Song, … Franklin W. Huang·Nature CommunicationsPeer-reviewed·Jun 17, 2025
- Morphometry and mechanical instability at the onset of epithelial bladder cancer
F. L. Lampart, R. Vetter, … D. Iber·bioRxiv·Aug 17, 2023