Abstract

Prostate cancer is the second most common cancer in men, for which there are no reliable biomarkers or targeted therapies. Here we demonstrate that elevated levels of Δ133TP53β isoform characterize prostate cancers with immune cell infiltration, particularly T cells and CD163+ macrophages. These cancers are associated with shorter progression-free survival, Gleason scores ≥ 7, and an immunosuppressive environment defined by a higher proportion of PD-1, PD-L1 and colony-stimulating factor 1 receptor (CSF1R) positive cells. Consistent with this, RNA-seq of tumours showed enrichment for pathways associated with immune signalling and cell migration. We further show a role for hypoxia and wild-type p53 in upregulating Δ133TP53 levels. Finally, AUC analysis showed that Δ133TP53β expression level alone predicted aggressive disease with 88% accuracy. Our data identify Δ133TP53β as a highly accurate prognostic factor for aggressive prostate cancer.

Details

Title
The Δ133p53β isoform promotes an immunosuppressive environment leading to aggressive prostate cancer
Author
Kazantseva, Marina 1 ; Mehta, Sunali 1 ; Eiholzer, Ramona A 2 ; Gimenez, Gregory 2 ; Bowie, Sara 2 ; Campbell, Hamish 3 ; Reily-Bell, Ashley L 2 ; Roth, Imogen 2 ; Sankalita Ray 2 ; Drummond, Catherine J 2 ; Reid, Glen 1 ; Joruiz, Sebastien M 4 ; Wiles, Anna 1 ; Morrin, Helen R 5 ; Reader, Karen L 6   VIAFID ORCID Logo  ; Hung, Noelyn A 2 ; Baird, Margaret A 2 ; Slatter, Tania L 1 ; Braithwaite, Antony W 7 

1  Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand; Maurice Wilkins Centre for Molecular Biodiscovery, Auckland, New Zealand 
2  Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand 
3  Children’s Medical Research Institute, University of Sydney, Camperdown, NSW, Australia 
4  Jacqui Wood Cancer Centre, Division of Cancer Research, University of Dundee, Dundee, UK 
5  Department of Pathology, University of Otago, Christchurch, New Zealand 
6  Department of Anatomy, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand 
7  Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand; Maurice Wilkins Centre for Molecular Biodiscovery, Auckland, New Zealand; Children’s Medical Research Institute, University of Sydney, Camperdown, NSW, Australia 
Pages
1-17
Publication year
2019
Publication date
Aug 2019
Publisher
Springer Nature B.V.
e-ISSN
20414889
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41419-019-1861-1
ProQuest document ID
2276821761
Copyright
© 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.