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Int. J. Mol. Sci. 2015, 16(10), 24369-24386; doi:10.3390/ijms161024369

Expression of Vitamin D Receptor (VDR) Positively Correlates with Survival of Urothelial Bladder Cancer Patients

1
Department of Tumour Pathology and Pathomorphology, Nicolaus Copernicus University Collegium Medicum in Bydgoszcz, Bydgoszcz 85-796, Poland
2
Department of Tumour Pathology and Pathomorphology, Oncology Centre–Prof. Franciszek Łukaszczyk Memorial Hospital, Bydgoszcz 85-796, Poland
3
Department of Urology, Oncology Centre–Prof. Franciszek Łukaszczyk Memorial Hospital, Bydgoszcz 85-796, Poland
4
Departments of Dermatology and Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
5
Department of Veteran Affairs (VA) Medical Center, Birmingham, AL 35294, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Roman Perez-Fernandez
Received: 6 August 2015 / Revised: 12 September 2015 / Accepted: 25 September 2015 / Published: 15 October 2015
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Abstract

Vitamin D3 shows tumoristatic and anticancer effects by acting through the vitamin D receptor (VDR), while hydroxylation of 25-hydroxyvitamin D3 at position 1α by CYP27B1 is an essential step in its activation. The expression of both the VDR and CYP27B1 has been found in many normal and cancer tissues, but there is a lack of information about its expression in human bladder cancers. The aim of the present research was to examine whether the expression of the VDR and CYP27B1 in bladder cancer was related to the prognostic markers and disease outcome. We analyzed VDR and CYP27B1 in samples of tumor and normal tissues obtained from 71 urinary bladder cancer patients. The highest VDR immunostaining was found in normal epithelium and was significantly lower in bladder cancer cells (p < 0.001 with Mann–Whitney U test). VDR expression was lowest in more advanced (pT2b–pT4) (p = 0.005 with Mann–Whitney U test) and metastasizing cancers (p < 0.05 and p = 0.004 with Mann–Whitney U test for nuclear and cytoplasmic VDR immunostaining, respectively). The lack of cytoplasmic and nuclear VDR was also related to shorter overall survival (for cytoplasmic VDR immunolocalization 13.3 vs. 55.3 months of survival, HR = 1.92, p = 0.04 and for nuclear VDR immunostaining 13.5 vs. 55.3 months of survival, HR = 2.47, p = 0.002 with Mantel-Cox test). In cases with the lack of high cytoplasmic VDR staining the non-classic differentiations (NDs) was observed in higher percentage of tumor area. CYP27B1 expression was lower in cancer cells than in normal epithelial cells (p = 0.03 with Mann–Whitney U test), but its expression did not correlate with tumor stage (pT), metastasizing, grade, mitotic activity or overall survival. In conclusion, expression of the VDR and CYP27B1 are deregulated in urothelial bladder cancers. Although our results showing a relationship between the decreased VDR expression and prognostic markers and survival time indicate potential usefulness of VDR as a new indicator of a poorer prognosis, further studies are needed in different patient cohorts by independent groups to validate this hypothesis. We also suggest that vitamin D-based therapies may represent an adjuvant strategy in treatment for bladder cancers expressing VDR. View Full-Text
Keywords: vitamin D receptor (VDR); urothelial bladder cancer; survival; vitamin D; CYP27B1 vitamin D receptor (VDR); urothelial bladder cancer; survival; vitamin D; CYP27B1
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Jóźwicki, W.; Brożyna, A.A.; Siekiera, J.; Slominski, A.T. Expression of Vitamin D Receptor (VDR) Positively Correlates with Survival of Urothelial Bladder Cancer Patients. Int. J. Mol. Sci. 2015, 16, 24369-24386.

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