Transcriptome sequencing and multi-plex imaging of prostate cancer microenvironment reveals a dominant role for monocytic cells in progression.
Computational Biology
/ methods
Disease Progression
Gene Expression Profiling
/ methods
High-Throughput Nucleotide Sequencing
Humans
Immunohistochemistry
Immunophenotyping
Kaplan-Meier Estimate
Male
Molecular Sequence Annotation
Monocytes
/ metabolism
Prognosis
Prostatic Neoplasms
/ diagnosis
Transcriptome
Tumor Microenvironment
/ genetics
Bayes
CAPRA-S
Cholesterol
Deconvolution
Differential gene expression
Epithelial
FACS
Immunohistochemistry
Macrophages
Microenvironment
Myeloid
PDL1
Prostate cancer
Transcriptomics
Journal
BMC cancer
ISSN: 1471-2407
Titre abrégé: BMC Cancer
Pays: England
ID NLM: 100967800
Informations de publication
Date de publication:
22 Jul 2021
22 Jul 2021
Historique:
received:
10
03
2021
accepted:
23
06
2021
entrez:
23
7
2021
pubmed:
24
7
2021
medline:
21
10
2021
Statut:
epublish
Résumé
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.
Sections du résumé
BACKGROUND
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
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
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.
Identifiants
pubmed: 34294073
doi: 10.1186/s12885-021-08529-6
pii: 10.1186/s12885-021-08529-6
pmc: PMC8296706
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
846Subventions
Organisme : National Health and Medical Research Council
ID : 1054618
Informations de copyright
© 2021. The Author(s).
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