Dynamic prostate cancer transcriptome analysis delineates the trajectory to disease progression
| العنوان: | Dynamic prostate cancer transcriptome analysis delineates the trajectory to disease progression |
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| المؤلفون: | Eugenia D’Antonio, Laura Di Rito, Silke Gillessen, Angela Rita Elia, Eugenio Zoni, Fernando Jermini, Arianna Vallerga, Mark A. Rubin, Jean-Philippe Theurillat, Holger Moch, Marco Bolis, Daniela Bossi, Andrea Rinaldi, Eva Corey, Arianna Calcinotto, George N. Thalmann, Simone Mosole, Marianna Kruithof-de Julio, Daniela Impellizzieri, Valentina Ceserani, Lukas Bubendorf, Martin Spahn, Ricardo Pereira Mestre, Flavio Stoffel, Matteo Ferrari, Manuela Cavalli, Peter Schraml |
| المصدر: | Nature Communications, Vol 12, Iss 1, Pp 1-15 (2021) Bolis, Marco; Bossi, Daniela; Vallerga, Arianna; Ceserani, Valentina; Cavalli, Manuela; Impellizzieri, Daniela; Di Rito, Laura; Zoni, Eugenio; Mosole, Simone; Elia, Angela Rita; Rinaldi, Andrea; Pereira Mestre, Ricardo; D'Antonio, Eugenia; Ferrari, Matteo; Stoffel, Flavio; Jermini, Fernando; Gillessen, Silke; Bubendorf, Lukas; Schraml, Peter; Calcinotto, Arianna; ... (2021). Dynamic prostate cancer transcriptome analysis delineates the trajectory to disease progression. Nature Communications, 12(1), p. 7033. Springer Nature 10.1038/s41467-021-26840-5 <http://dx.doi.org/10.1038/s41467-021-26840-5Test> Nature Communications |
| بيانات النشر: | Springer Science and Business Media LLC, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Male, Tumour heterogeneity, Science, Macrophage polarization, General Physics and Astronomy, 610 Medicine & health, Biology, Article, General Biochemistry, Genetics and Molecular Biology, Transcriptome, Mice, Prostate cancer, Atlases as Topic, Downregulation and upregulation, Cell Line, Tumor, medicine, Animals, Humans, Enhancer of Zeste Homolog 2 Protein, Principal Component Analysis, Multidisciplinary, Gene Expression Profiling, Macrophages, EZH2, Polycomb Repressive Complex 2, Prostate, Prostatic Neoplasms, General Chemistry, medicine.disease, M2 Macrophage, Neoplasm Proteins, G2 Phase Cell Cycle Checkpoints, Gene Expression Regulation, Neoplastic, Tumor progression, Cancer cell, Disease Progression, Cancer research, Heterografts, Single-Cell Analysis, Signal Transduction |
| الوصف: | Comprehensive genomic studies have delineated key driver mutations linked to disease progression for most cancers. However, corresponding transcriptional changes remain largely elusive because of the bias associated with cross-study analysis. Here, we overcome these hurdles and generate a comprehensive prostate cancer transcriptome atlas that describes the roadmap to tumor progression in a qualitative and quantitative manner. Most cancers follow a uniform trajectory characterized by upregulation of polycomb-repressive-complex-2, G2-M checkpoints, and M2 macrophage polarization. Using patient-derived xenograft models, we functionally validate our observations and add single-cell resolution. Thereby, we show that tumor progression occurs through transcriptional adaption rather than a selection of pre-existing cancer cell clusters. Moreover, we determine at the single-cell level how inhibition of EZH2 - the top upregulated gene along the trajectory – reverts tumor progression and macrophage polarization. Finally, a user-friendly web-resource is provided enabling the investigation of dynamic transcriptional perturbations linked to disease progression. Transcriptional changes during prostate cancer progression are not yet fully understood. Here, the authors integrate a transcriptomics atlas of prostate cancer and validate it with preclinical models and single-cell RNA-seq, revealing the role of EZH2 and macrophage polarisation in tumour progression. |
| وصف الملف: | application/pdf |
| تدمد: | 2041-1723 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ab29dd83acce3fc6cf1e71d948c9c7ffTest https://doi.org/10.1038/s41467-021-26840-5Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....ab29dd83acce3fc6cf1e71d948c9c7ff |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
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