Transcriptional signals of transformation in human cancer

人类癌症转化的转录信号

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作者:Gerda Kildisiute #, Maria Kalyva #, Rasa Elmentaite, Stijn van Dongen, Christine Thevanesan, Alice Piapi, Kirsty Ambridge, Elena Prigmore, Muzlifah Haniffa, Sarah A Teichmann, Karin Straathof, Isidro Cortés-Ciriano, Sam Behjati, Matthew D Young0

Background

As normal cells transform into cancers, their cell state changes, which may drive cancer cells into a stem-like or more primordial, foetal, or embryonic cell state. The transcriptomic profile of this final state may encode information about cancer's origin and how cancers relate to their normal cell counterparts.

Conclusions

Our findings provide a nuanced picture of transformation in human cancer, indicating cancer-specific rather than universal patterns of transformation pervade adult epithelial cancers.

Methods

Here, we used single-cell atlases to study cancer transformation in transcriptional terms. We utilised bulk transcriptomes across a wide spectrum of adult and childhood cancers, using a previously established method to interrogate their relationship to normal cell states. We extend and validate these findings using single-cell cancer transcriptomes and organ-specific atlases of colorectal and liver cancer.

Results

Our bulk transcriptomic data reveals that adult cancers rarely return to an embryonic state, but that a foetal state is a near-universal feature of childhood cancers. This finding was confirmed with single-cell cancer transcriptomes. Conclusions: Our findings provide a nuanced picture of transformation in human cancer, indicating cancer-specific rather than universal patterns of transformation pervade adult epithelial cancers.

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