Dynamic prostate cancer transcriptome analysis delineates the trajectory to disease progression.

Autor: Bolis M; Faculty of Biomedical Sciences, Institute of Oncology Research, USI, Bellinzona, TI, 6500, Switzerland. marco.bolis@ior.usi.ch.; Computational Oncology Unit, Department of Oncology, Istituto di Richerche Farmacologiche 'Mario Negri' IRCCS, 20156, Milano, Italy. marco.bolis@ior.usi.ch.; Bioinformatics Core Unit, Swiss Institute of Bioinformatics, TI, 6500, Bellinzona, Switzerland. marco.bolis@ior.usi.ch., Bossi D; Faculty of Biomedical Sciences, Institute of Oncology Research, USI, Bellinzona, TI, 6500, Switzerland., Vallerga A; Faculty of Biomedical Sciences, Institute of Oncology Research, USI, Bellinzona, TI, 6500, Switzerland.; Bioinformatics Core Unit, Swiss Institute of Bioinformatics, TI, 6500, Bellinzona, Switzerland., Ceserani V; Faculty of Biomedical Sciences, Institute of Oncology Research, USI, Bellinzona, TI, 6500, Switzerland., Cavalli M; Faculty of Biomedical Sciences, Institute of Oncology Research, USI, Bellinzona, TI, 6500, Switzerland., Impellizzieri D; Faculty of Biomedical Sciences, Institute of Oncology Research, USI, Bellinzona, TI, 6500, Switzerland., Di Rito L; Computational Oncology Unit, Department of Oncology, Istituto di Richerche Farmacologiche 'Mario Negri' IRCCS, 20156, Milano, Italy., Zoni E; Department of Biomedical Research, University of Bern, 3008, Bern, Switzerland., Mosole S; Faculty of Biomedical Sciences, Institute of Oncology Research, USI, Bellinzona, TI, 6500, Switzerland., Elia AR; Faculty of Biomedical Sciences, Institute of Oncology Research, USI, Bellinzona, TI, 6500, Switzerland., Rinaldi A; Faculty of Biomedical Sciences, Institute of Oncology Research, USI, Bellinzona, TI, 6500, Switzerland., Pereira Mestre R; Oncology Institute of Southern Switzerland, Bellinzona, TI, 6500, Switzerland., D'Antonio E; Oncology Institute of Southern Switzerland, Bellinzona, TI, 6500, Switzerland., Ferrari M; Urology Department, Ente Ospedaliero Cantonale, Bellinzona, TI, Switzerland., Stoffel F; Urology Department, Ente Ospedaliero Cantonale, Bellinzona, TI, Switzerland., Jermini F; Urology Department, Ente Ospedaliero Cantonale, Bellinzona, TI, Switzerland., Gillessen S; Oncology Institute of Southern Switzerland, Bellinzona, TI, 6500, Switzerland.; Faculty of Biomedical Sciences, University of Southern Switzerland (USI), TI, 6900, Lugano, Switzerland., Bubendorf L; Institute of Surgical Pathology, University Hospital Basel, 4031, Basel, Switzerland., Schraml P; Department of Pathology, University Hospital Zurich, 8091, Zurich, Switzerland., Calcinotto A; Faculty of Biomedical Sciences, Institute of Oncology Research, USI, Bellinzona, TI, 6500, Switzerland., Corey E; Department of Urology, University of Washington, Seattle, WA, 98195, USA., Moch H; Department of Pathology, University Hospital Zurich, 8091, Zurich, Switzerland., Spahn M; Lindenhofspital Bern, Prostate Center Bern, 3012, Bern, Switzerland., Thalmann G; Department of Biomedical Research, University of Bern, 3008, Bern, Switzerland.; Department of Urology, Inselspital, Bern University Hospital, 3010, Bern, Switzerland., Kruithof-de Julio M; Department of Biomedical Research, University of Bern, 3008, Bern, Switzerland.; Department of Urology, Inselspital, Bern University Hospital, 3010, Bern, Switzerland., Rubin MA; Department of Biomedical Research, University of Bern, 3008, Bern, Switzerland.; Bern Center for Precision Medicine, University of Bern and Inselspital, 3012, Bern, Switzerland., Theurillat JP; Faculty of Biomedical Sciences, Institute of Oncology Research, USI, Bellinzona, TI, 6500, Switzerland. jean-philippe.theurillat@ior.usi.ch.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2021 Dec 02; Vol. 12 (1), pp. 7033. Date of Electronic Publication: 2021 Dec 02.
DOI: 10.1038/s41467-021-26840-5
Abstrakt: 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.
(© 2021. The Author(s).)
Databáze: MEDLINE
Externí odkaz: