Journal article

Transcriptome sequencing and multi-plex imaging of prostate cancer microenvironment reveals a dominant role for monocytic cells in progression

Stefano Mangiola, Patrick McCoy, Martin Modrak, Fernando Souza-Fonseca-Guimaraes, Daniel Blashki, Ryan Stuchbery, Simon P Keam, Michael Kerger, Ken Chow, Chayanica Nasa, Melanie Le Page, Natalie Lister, Simon Monard, Justin Peters, Phil Dundee, Scott G Williams, Anthony J Costello, Paul J Neeson, Bhupinder Pal, Nicholas D Huntington Show all

BMC CANCER | BMC | Published : 2021

Abstract

BACKGROUND: Prostate cancer is caused by genomic aberrations in normal epithelial cells, however clinical translation of findings from analyses of cancer cells alone has been very limited. A deeper understanding of the tumour microenvironment is needed to identify the key drivers of disease progression and reveal novel therapeutic opportunities. RESULTS: In this study, the experimental enrichment of selected cell-types, the development of a Bayesian inference model for continuous differential transcript abundance, and multiplex immunohistochemistry permitted us to define the transcriptional landscape of the prostate cancer microenvironment along the disease progression axis. An important rol..

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Grants

Awarded by Australian National Health and Medical Research Council (NHMRC)


Awarded by NHMRC Senior Research Fellowship


Awarded by Priority-driven Collaborative Cancer Research Scheme


Awarded by ELIXIR CZ research infrastructure project (MEYS)


Funding Acknowledgements

SM was supported by the David Mayor PhD Scholarship from the Prostate Cancer Research Foundation. SM and ATP were supported by the Lorenzo and Pamela Galli Charitable Trust. ATP was supported by an Australian National Health and Medical Research Council (NHMRC) Program Grant (1054618) and NHMRC Senior Research Fellowship (1116955). ATP, CH and NC were supported by Movember. KC was supported by a Postgraduate Medical Research Scholarship from the Prostate Cancer Research Fund and the Australian Government Research Training Program Scholarship provided by the Australian Commonwealth Government and the University of Melbourne. NDH was a recipient of a Melanoma Research Grant from the Harry J Lloyd Charitable Trust. FSFG was supported by grant #1158085, awarded through the Priority-driven Collaborative Cancer Research Scheme and funded by Cure Cancer Australia with the assistance of Cancer Australia. MM was supported by the ELIXIR CZ research infrastructure project (MEYS Grant No: LM2015047), including access to computing and storage facilities. NMC was supported by a David Bickart Clinician Research Fellowship from the Faculty of Medicine, Dentistry and Health Sciences at the University of Melbourne and the Movember Distinguished Gentleman's Ride Clinician Scientist Award through the Prostate Cancer Foundation of Australia's Research Programme. The research benefitted from support from the Victorian State Government Operational Infrastructurte Support and Australian Government NHMRC Independent Research Institute Infrastructure Support. The funding body has no role in the design of the study and collection, analysis, and interpretation of data nor in writing the manuscript.