Human phosphodiesterase 4D7 (PDE4D7) expression is increased in TMPRSS2-ERG positive primary prostate cancer and independently adds to a reduced risk of post-surgical disease progression

Bottcher, R. et al. (2015) Human phosphodiesterase 4D7 (PDE4D7) expression is increased in TMPRSS2-ERG positive primary prostate cancer and independently adds to a reduced risk of post-surgical disease progression. British Journal of Cancer, 113, pp. 1502-1511. (doi:10.1038/bjc.2015.335) (PMID:PMID:26575)

[img]
Preview
Text
109653.pdf - Published Version
Available under License Creative Commons Attribution Non-commercial.

3MB

Abstract

background: There is an acute need to uncover biomarkers that reflect the molecular pathologies, underpinning prostate cancer progression and poor patient outcome. We have previously demonstrated that in prostate cancer cell lines PDE4D7 is downregulated in advanced cases of the disease. To investigate further the prognostic power of PDE4D7 expression during prostate cancer progression and assess how downregulation of this PDE isoform may affect disease outcome, we have examined PDE4D7 expression in physiologically relevant primary human samples. methods: About 1405 patient samples across 8 publically available qPCR, Affymetrix Exon 1.0 ST arrays and RNA sequencing data sets were screened for PDE4D7 expression. The TMPRSS2-ERG gene rearrangement status of patient samples was determined by transformation of the exon array and RNA seq expression data to robust z-scores followed by the application of a threshold >3 to define a positive TMPRSS2-ERG gene fusion event in a tumour sample. results: We demonstrate that PDE4D7 expression positively correlates with primary tumour development. We also show a positive association with the highly prostate cancer-specific gene rearrangement between TMPRSS2 and the ETS transcription factor family member ERG. In addition, we find that in primary TMPRSS2-ERG-positive tumours PDE4D7 expression is significantly positively correlated with low-grade disease and a reduced likelihood of progression after primary treatment. Conversely, PDE4D7 transcript levels become significantly decreased in castration resistant prostate cancer (CRPC). conclusions: We further characterise and add physiological relevance to PDE4D7 as a novel marker that is associated with the development and progression of prostate tumours. We propose that the assessment of PDE4D7 levels may provide a novel, independent predictor of post-surgical disease progression.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Houslay, Professor Miles and Baillie, Professor George
Authors: Bottcher, R., Henderson, D. J. P., Dulla, K., van Strijp, D., Waanders, L. F., Tevz, G., Lehman, M. L., Merkle, D., van Leenders, G. J. L. H., Baillie, G. S., Jenster, G., Houslay, M. D., and Hoffmann, R.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Neuroscience and Psychology
Journal Name:British Journal of Cancer
Publisher:Nature Publishing Group
ISSN:0007-0920
ISSN (Online):1532-1827
Copyright Holders:Copyright © 2015 Cancer Research UK
First Published:First published in British Journal of Cancer 113:1502-1511
Publisher Policy:Reproduced under a Creative Commons License

University Staff: Request a correction | Enlighten Editors: Update this record

Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
518761BBSRC Industrial Case PhD Studentship 2009.George BaillieBiotechnology and Biological Sciences Research Council (BBSRC)BB/G01647X/1RI NEUROSCIENCE & PSYCHOLOGY