Rxivist logo

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.

Download data

  • Downloaded 195 times
  • Download rankings, all-time:
    • Site-wide: 147,996
    • In cancer biology: 4,551
  • Year to date:
    • Site-wide: 12,734
  • Since beginning of last month:
    • Site-wide: 16,959

Altmetric data

Downloads over time

Distribution of downloads per paper, site-wide