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

The prostanoid thromboxane (TX)A(2) plays a central role in haemostasis and is increasingly implicated in cancer progression. TXA(2) signals through two T Prostanoid receptor (TP) isoforms termed TP alpha and TP beta, 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 TP alpha and TP beta isoforms in tumour microarrays of the benign prostate and different pathological (Gleason) grades of prostate cancer (PCa). Expression of TP beta was significantly increased in PCa relative to benign tissue and strongly correlated with increasing Gleason grade. Furthermore, higher TP beta expression was associated with increased risk of biochemical recurrence (BCR) and significantly shorter disease-free survival time in patients post-surgery. While TP alpha was more variably expressed than TP beta in PCa, increased/high TP alpha 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 TP alpha and TP beta, respectively, both in benign prostate and in clinically-derived tissue representative of precursor lesions and progressive stages of PCa. Collectively, TP alpha and TP beta 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 TP beta, or a combination of TP alpha/TP beta, expression levels may have significant clinical potential as a diagnostic biomarker and predictor of PCa disease recurrence.