Transcriptome sequencing and multi-plex imaging of prostate cancer microenvironment reveals a dominant role for monocytic cells in progression
Autor: | Stefano Mangiola, Martin Modrak, Chayanica Nasa, Natalie Lister, Phil Dundee, Justin S. Peters, Paul J Neeson, Bhupinder Pal, Daniel Blashki, Niall M. Corcoran, Christopher M. Hovens, Anthony J. Costello, Nicholas D. Huntington, Ryan Stuchbery, Scott Williams, Simon Monard, Simon P. Keam, Fernando Souza-Fonseca-Guimaraes, Ken Chow, Patrick McCoy, Michael Kerger, Melanie Le Page, Anthony T. Papenfuss |
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Rok vydání: | 2021 |
Předmět: |
Myeloid
Male 0301 basic medicine Cancer Research Kaplan-Meier Estimate Deconvolution Disease Monocytes Transcriptome Prostate cancer 0302 clinical medicine Prostate Tumor Microenvironment Differential gene expression RC254-282 High-Throughput Nucleotide Sequencing Neoplasms. Tumors. Oncology. Including cancer and carcinogens Prognosis Immunohistochemistry Cholesterol medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Disease Progression Research Article Bayes Microenvironment FACS Biology Immunophenotyping 03 medical and health sciences PDL1 Genetics medicine Humans Transcriptomics Tumor microenvironment Macrophages Gene Expression Profiling Computational Biology Prostatic Neoplasms Cancer Molecular Sequence Annotation medicine.disease Gene expression profiling CAPRA-S 030104 developmental biology Cancer cell Cancer research Epithelial |
Zdroj: | BMC Cancer, Vol 21, Iss 1, Pp 1-18 (2021) BMC Cancer |
ISSN: | 1471-2407 |
Popis: | 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 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. Conclusions 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. |
Databáze: | OpenAIRE |
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