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Emergence of an adaptive epigenetic cell state in human bladder urothelial carcinoma evolution

Xiao, Y.; Jin, W.; Qian, K.; Wu, K.; Wang, G.; Jiang, W.; Cao, R.; Ju, L.; Zhao, Y.; Zheng, H.; Liu, T.; Chang, L.; Xu, Z.; Wang, T.; Luo, J.; Shan, L.; Yu, F.; Chen, X.; Liu, D.; Cao, H.; Yang, Z.; Li, S.; Shi, H.; Guo, Z.; Gong, Y.; Liu, N.; Li, S.; Wang, Y.; Cao, X.; Ding, W.; Zhou, W.; Cui, D.; Tian, Y.; Ji, C.; Luo, Y.; Hong, X.; Ma, H.; Chen, F.; Peng, M.; Zhang, Y.; Wang, X.

2021-11-02 cancer biology
10.1101/2021.10.30.466556 bioRxiv
Show 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.

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"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.