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

0544993 - MBÚ 2022 RIV GB eng J - Journal Article
Mangiola, S. - McCoy, P. - Modrák, Martin - Souza-Fonseca-Guimaraes, F. - Blashki, D. - Stuchbery, R. - Keam, S. P. - Kerger, M. - Chow, K. - Nasa, C. - Le Page, M. - Lister, N. - Monard, S. - Peters, J. - Dundee, P. - Williams, S. G. - Costello, A. J. - Neeson, P. J. - Pal, B. - Huntington, N. D. - Corcoran, N. M. - Papenfuss, A. T. - Hovens, C. M.
Transcriptome sequencing and multi-plex imaging of prostate cancer microenvironment reveals a dominant role for monocytic cells in progression.
Bmc Cancer. Roč. 21, č. 1 (2021), č. článku 846. E-ISSN 1471-2407
R&D Projects: GA MŠMT(CZ) LM2015047
Institutional support: RVO:61388971
Keywords : Prostate cancer * Transcriptomics * facs * Immunohistochemistry * Deconvolution * Bayes * Differential gene expression * capra-s * Microenvironment * Epithelial * Myeloid * Macrophages * Cholesterol * pdl1
OECD category: Oncology
Impact factor: 4.638, year: 2021
Method of publishing: Open access
https://bmccancer.biomedcentral.com/articles/10.1186/s12885-021-08529-6

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.
Permanent Link: http://hdl.handle.net/11104/0321780