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Expression of the TPa and TPβ isoforms of the thromboxane prostanoid receptor (TP) in prostate cancer : Clinical significance and diagnostic potential

Mulvaney, Eamon P.; Shilling, Christine; Eivers, Sarah B.; Perry, Antoinette S.; Bjartell, Anders LU ; Kay, Elaine W.; William Watson, R. and Kinsella, B. Therese (2016) In Oncotarget 7(45). p.73171-73187
Abstract

The prostanoid thromboxane (TX)A2 plays a central role in haemostasis and is increasingly implicated in cancer progression. TXA2 signals through two T Prostanoid receptor (TP) isoforms termed TPa and TPβ, with both encoded by the TBXA2R gene. Despite exhibiting several functional and regulatory differences, the role of the individual TP isoforms in neoplastic diseases is largely unknown. This study evaluated expression of the TPa and TPβ isoforms in tumour microarrays of the benign prostate and different pathological (Gleason) grades of prostate cancer (PCa). Expression of TPβ was significantly increased in PCa relative to benign tissue and strongly correlated with increasing Gleason grade. Furthermore, higher TPβ expression was... (More)

The prostanoid thromboxane (TX)A2 plays a central role in haemostasis and is increasingly implicated in cancer progression. TXA2 signals through two T Prostanoid receptor (TP) isoforms termed TPa and TPβ, with both encoded by the TBXA2R gene. Despite exhibiting several functional and regulatory differences, the role of the individual TP isoforms in neoplastic diseases is largely unknown. This study evaluated expression of the TPa and TPβ isoforms in tumour microarrays of the benign prostate and different pathological (Gleason) grades of prostate cancer (PCa). Expression of TPβ was significantly increased in PCa relative to benign tissue and strongly correlated with increasing Gleason grade. Furthermore, higher TPβ expression was associated with increased risk of biochemical recurrence (BCR) and significantly shorter disease-free survival time in patients post-surgery. While TPa was more variably expressed than TPβ in PCa, increased/high TPa expression within the tumour also trended toward increased BCR and shorter diseasefree survival time. Comparative genomic CpG DNA methylation analysis revealed substantial differences in the extent of methylation of the promoter regions of the TBXA2R that specifically regulate expression of TPa and TPβ, respectively, both in benign prostate and in clinically-derived tissue representative of precursor lesions and progressive stages of PCa. Collectively, TPa and TPβ expression is differentially regulated both in the benign and tumourigenic prostate, and coincides with clinical pathology and altered CpG methylation of the TBXA2R gene. Analysis of TPβ, or a combination of TPa/TPβ, expression levels may have significant clinical potential as a diagnostic biomarker and predictor of PCa disease recurrence.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cancer, Prostanoid, Prostate, Receptor, Thromboxane
in
Oncotarget
volume
7
issue
45
pages
17 pages
publisher
Impact Journals, LLC
external identifiers
  • scopus:84995745167
  • wos:000387452100058
ISSN
1949-2553
DOI
10.18632/oncotarget.12256
language
English
LU publication?
yes
id
defffcf5-9eef-459b-b8cd-1dacaf7fd214
date added to LUP
2016-12-05 10:21:21
date last changed
2017-10-29 04:54:58
@article{defffcf5-9eef-459b-b8cd-1dacaf7fd214,
  abstract     = {<p>The prostanoid thromboxane (TX)A2 plays a central role in haemostasis and is increasingly implicated in cancer progression. TXA2 signals through two T Prostanoid receptor (TP) isoforms termed TPa and TPβ, with both encoded by the TBXA2R gene. Despite exhibiting several functional and regulatory differences, the role of the individual TP isoforms in neoplastic diseases is largely unknown. This study evaluated expression of the TPa and TPβ isoforms in tumour microarrays of the benign prostate and different pathological (Gleason) grades of prostate cancer (PCa). Expression of TPβ was significantly increased in PCa relative to benign tissue and strongly correlated with increasing Gleason grade. Furthermore, higher TPβ expression was associated with increased risk of biochemical recurrence (BCR) and significantly shorter disease-free survival time in patients post-surgery. While TPa was more variably expressed than TPβ in PCa, increased/high TPa expression within the tumour also trended toward increased BCR and shorter diseasefree survival time. Comparative genomic CpG DNA methylation analysis revealed substantial differences in the extent of methylation of the promoter regions of the TBXA2R that specifically regulate expression of TPa and TPβ, respectively, both in benign prostate and in clinically-derived tissue representative of precursor lesions and progressive stages of PCa. Collectively, TPa and TPβ expression is differentially regulated both in the benign and tumourigenic prostate, and coincides with clinical pathology and altered CpG methylation of the TBXA2R gene. Analysis of TPβ, or a combination of TPa/TPβ, expression levels may have significant clinical potential as a diagnostic biomarker and predictor of PCa disease recurrence.</p>},
  author       = {Mulvaney, Eamon P. and Shilling, Christine and Eivers, Sarah B. and Perry, Antoinette S. and Bjartell, Anders and Kay, Elaine W. and William Watson, R. and Kinsella, B. Therese},
  issn         = {1949-2553},
  keyword      = {Cancer,Prostanoid,Prostate,Receptor,Thromboxane},
  language     = {eng},
  number       = {45},
  pages        = {73171--73187},
  publisher    = {Impact Journals, LLC},
  series       = {Oncotarget},
  title        = {Expression of the TPa and TPβ isoforms of the thromboxane prostanoid receptor (TP) in prostate cancer : Clinical significance and diagnostic potential},
  url          = {http://dx.doi.org/10.18632/oncotarget.12256},
  volume       = {7},
  year         = {2016},
}