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标题：Emergence of hybrid states of stem-like cancer cells correlates with poor prognosis in oral cancer
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作者：Kavya Vipparthi ; Kishore Hari ; Priyanka Chakraborty 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2022
卷号：25
期号：5
页码：1-27
DOI：10.1016/j.isci.2022.104317
语种：English
出版社：Elsevier
摘要：SummaryCancer cell state transitions emerged as powerful mechanisms responsible for drug tolerance and overall poor prognosis; however, evidences were largely missing in oral cancer. Here, by multiplexing phenotypic markers of stem-like cancer cells (SLCCs); CD44, CD24 and aldehyde dehydrogenase (ALDH), we characterized diversity among multiple oral tumor tissues and cell lines. Two distinct patterns of spontaneous transitions with stochastic bidirectional interconversions on ‘ALDH-axis’, and unidirectional non-interconvertible transitions on ‘CD24-axis’ were observed. Interestingly, plastic ‘ALDH-axis’ was harnessed by cells to adapt to a Cisplatin tolerant state. Furthermore, phenotype-specific RNA sequencing suggested the possible maintenance of intermediate hybrid cell states maintaining stemness within the differentiating subpopulations. Importantly, survival analysis with subpopulation-specific gene sets strongly suggested that cell-state transitions may drive non-genetic heterogeneity, resulting in poor prognosis. Therefore, we have described the phenotypic-composition of heterogeneous subpopulations critical for global tumor behavior in oral cancer; which may provide prerequisite knowledge for treatment strategies.Graphical abstractDisplay OmittedHighlights•Demonstrated population trajectory driven non-genetic heterogeneity in oral cancer•Created transition maps for subpopulations using discrete time Markov chain model•Demonstrated maintenance of stemness in cells undergoing differentiation•Uniquely expressed genes of these subpopulations associated with disease prognosisImmunology; Biophysics; Cancer systems biology; Cancer, Stemness