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

Mangiola, S; McCoy, P; Modrak, M; Souza-Fonseca-Guimaraes, F; Blashki, D; Stuchbery, R; Keam, SP; Kerger, M; Chow, K; Nasa, C; Le Page, M; Lister, N; Monard, S; Peters, J; Dundee, P; Williams, SG; Costello, AJ; Neeson, PJ; Pal, B; Huntington, ND; Corcoran, NM; Papenfuss, AT; Hovens, CM

Author(s): Mangiola, S; McCoy, P; Modrak, M; Souza-Fonseca-Guimaraes, F; Blashki, D; Stuchbery, R; Keam, SP; Kerger, M; Chow, K; Nasa, C; Le Page, M; Lister, N; Monard, S; Peters, J; Dundee, P; Williams, SG; Costello, AJ; Neeson, PJ; Pal, B; Huntington, ND; Corcoran, NM; Papenfuss, AT; Hovens, CM;
Details: Publication Year 2021-07-22,Volume 21,Issue #1,Page 846
Journal Title: BMC Cancer
Abstract: 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.
Publisher: BMC
Keywords: Bayes; Capra-s; Cholesterol; Deconvolution; Differential gene expression; Epithelial; Facs; Immunohistochemistry; Macrophages; Microenvironment; Myeloid; Pdl1; Prostate cancer; Transcriptomics
Research Division(s): Bioinformatics
PubMed ID: 34294073
Publisher's Version: https://doi.org/10.1186/s12885-021-08529-6
Open Access at Publisher's Site: https://doi.org/10.1186/s12885-021-08529-6
Terms of Use/Rights Notice: Refer to copyright notice on published article.
Documents: Mangiola S et al_BMC Cancer_2021.pdf - (3.16MB, application/pdf)

Creation Date: 2021-08-16 10:40:47

Last Modified: 2021-08-16 11:15:51