生物
前列腺癌
癌症的体细胞进化
遗传异质性
肿瘤进展
遗传学
细胞
色丛
癌症研究
癌症
计算生物学
核糖核酸
转录调控
干细胞
转录因子
表型
基因
PCA3系列
作者
Guangzhe Ge,Yang Han,Jianye Zhang,Xinxin Li,Xiaodan Liu,Yanqing Gong,Zhentao Lei,Jie Wang,Weijie Zhu,Yangyang Xu,Yue Peng,Jianhua Deng,Zhenan Bao,Xuesong Li,Liqun Zhou,Huiying He,Weimin Ci
标识
DOI:10.1002/advs.202105530
摘要
Prostate cancer (PCa) is a complex disease. An ongoing accumulation of mutations results in increased genetic diversity, with the tumor acquiring distinct subclones. However, non-genetic intra-tumoral heterogeneity, the cellular differentiation state and the interplay between subclonal evolution and transcriptional heterogeneity are poorly understood. Here, the authors perform single-cell RNA sequencing from 14 untreated PCa patients. They create an extensive cell atlas of the PCa patients and mapped developmental states onto tumor subclonal evolution. They identify distinct subclones across PCa patients and then stratify tumor cells into four transcriptional subtypes, EMT-like (subtype 0), luminal A-like (subtype 1), luminal B/C-like (subtype 2), and basal-like (subtype 3). These subtypes are hierarchically organized into stem cell-like and differentiated status. Strikingly, multiple subclones within a single primary tumor present with distinct combinations of preferential subtypes. In addition, subclones show different communication strengths with other cell types within the tumor ecosystem, which may modulate the distinct transcriptional subtypes of the subclones. Notably, by integrating TCGA data, they discover that both tumor cell transcriptional heterogeneity and cellular ecosystem diversity correlate with features of a poor prognosis. Collectively, their study provides the analysis of subclonal and transcriptional heterogeneity and its implication for patient prognosis.
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