Author:
Xiao Yu,Jin Wan,Qian Kaiyu,Wu Kai,Wang Gang,Jiang Wei,Cao Rui,Ju Lingao,Zhao Yan,Zheng Hang,Liu Tongzu,Chang Luyuan,Xu Zilin,Wang Ting,Luo Jun,Shan Liuying,Yu Fang,Chen Xintong,Liu Dongmei,Cao Hong,Yang Zhonghua,Li Sheng,Shi Hongjie,Guo Zhongqiang,Gong Yan,Liu Nan,Li Shenjuan,Wang Yejinpeng,Cao Xinyue,Ding Wenjun,Zhou Wei,Cui Diansheng,Tian Ye,Ji Chundong,Luo Yongwen,Hong Xin,Ma Haoli,Chen Fangjin,Peng Minsheng,Zhang Yi,Wang Xinghuan
Abstract
AbstractIntratumor 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.
Publisher
Cold Spring Harbor Laboratory
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献