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Title: Transcriptome sequencing and multi-plex imaging of prostate cancer microenvironment reveals a dominant role for monocytic cells in progression.
Austin Authors: Mangiola, Stefano;McCoy, Patrick;Modrak, Martin;Souza-Fonseca-Guimaraes, Fernando;Blashki, Daniel;Stuchbery, Ryan;Keam, Simon P;Kerger, Michael;Chow, Ken;Nasa, Chayanica;Le Page, Melanie;Lister, Natalie;Monard, Simon;Peters, Justin;Dundee, Phil;Williams, Scott G;Costello, Anthony J;Neeson, Paul J;Pal, Bhupinder;Huntington, Nicholas D;Corcoran, Niall M;Papenfuss, Anthony T;Hovens, Christopher M
Affiliation: Olivia Newton-John Cancer Research Institute
University of Queensland Diamantina Institute, Translational Research Institute, University of Queensland, Brisbane, QLD, Australia
The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria, Australia
Flow Cytometry Facility, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
Epworth Center of Cancer Research, Clayton, Victoria, Australia
Cancer Program, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia
Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia
Department of Surgery, The University of Melbourne, Parkville, Victoria, Australia
Department of Urology, Royal Melbourne Hospital, Parkville, Victoria, Australia
Department of Urology, Frankston Hospital, Frankston, Victoria, Australia
Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
Department of Medical Biology, University of Melbourne, Melbourne, Victoria, Australia
Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia
Peter MacCallum Cancer Centre, Melbourne, VIC, 3000, Australia
School of Mathematics and Statistics, University of Melbourne, Melbourne, VIC, 3010, Australia
Institute of Microbiology of the Czech Academy of Sciences, Prague, Czech Republic
Issue Date: 22-Jul-2021
Date: 2021-07-22
Publication information: BMC Cancer 2021; 21(1): 846
Abstract: 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. 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 role of monocytes and macrophages in prostate cancer progression and disease recurrence was uncovered, supported by both transcriptional landscape findings and by differential tissue composition analyses. These findings were corroborated and validated by spatial analyses at the single-cell level using multiplex immunohistochemistry. This study advances our knowledge concerning the role of monocyte-derived recruitment in primary prostate cancer, and supports their key role in disease progression, patient survival and prostate microenvironment immune modulation.
DOI: 10.1186/s12885-021-08529-6
ORCID: 0000-0002-1102-8506
Journal: BMC Cancer
PubMed URL: 34294073
Type: Journal Article
Subjects: Bayes
Differential gene expression
Prostate cancer
Appears in Collections:Journal articles

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