Expression of the TPα and TPβ isoforms of the thromboxane prostanoid receptor (TP) in prostate cancer: clinical significance and diagnostic potential
Metrics: PDF 1535 views | HTML 3290 views | ?
Eamon P. Mulvaney1, Christine Shilling3, Sarah B. Eivers1, Antoinette S. Perry1, Anders Bjartell4, Elaine W. Kay3, R. William Watson2, B. Therese Kinsella1
1UCD School of Biomolecular and Biomedical Science, University College Dublin, Belfield, Dublin, Ireland
2UCD School of Medicine, UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin, Ireland
3Department of Pathology, Beaumont Hospital and Royal College of Surgeons, Dublin, Ireland
4Department of Translational Medicine, Division of Urological Cancers, Skåne University Hospital Malmö, Lund University, Sweden
B. Therese Kinsella, email: [email protected]
Keywords: thromboxane, receptor, prostate, cancer, prostanoid
Received: June 09, 2016 Accepted: September 19, 2016 Published: September 26, 2016
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 TPα 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 TPα 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 TPα was more variably expressed than TPβ in PCa, increased/high TPα expression within the tumour also trended toward increased BCR and shorter disease-free 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 TPα and TPβ, respectively, both in benign prostate and in clinically-derived tissue representative of precursor lesions and progressive stages of PCa. Collectively, TPα 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 TPα/TPβ, expression levels may have significant clinical potential as a diagnostic biomarker and predictor of PCa disease recurrence.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.