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
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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