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

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.

Vitamin D-Related Gene Polymorphisms, Plasma 25-Hydroxy-Vitamin D, Cigarette Smoke and Non-Small Cell Lung Cancer (NSCLC) Risk

“…Because of its important role in vitamin D metabolism and blood Ca 2+ homeostasis, trivial changes in vitamin D hydroxylation activity could alter disease pathogenesis and outcome. Additionally, it exerts its oncogenic activities through its expressed protein in various cancers [56,57]. There is growing evidence that vitamin D may reduce the risk of developing NSCLC and that higher levels of vitamin D may be associated with better prognosis and improved outcome.…”

On the relationship between VDR, RORα and RORγ receptors expression and HIF1‐α levels in human melanomas

“…Formalin‐fixed paraffin‐embedded 4 µm section was immunostained and evaluated as previously described . Briefly, heat‐induced antigen retrieval was performed using Tris/EDTA buffer and microwave heating for VDR immunostaining, Target Retrieval Solution, pH 9 and PT Link device (Dako) for FoxP3 immunostaining and Target Retrieval Solution, pH 9 and PT Link device for other antibodies.…”

“…An observer analysing immunostained sections was blinded for detailed histopathological diagnosis, malignancy grade/stage and other clinical data, as previously described . Briefly, the staining intensity was evaluated with reference to immunostaining of epidermal cells for VDR, RORα, RORγ, CYP27B1, lymph node lymphocytes for FoxP3, kidney cells for CYP24A1, breast cancer cells for HIF‐1α, scored as strong.…”

Neurological manifestations of Vitamin D defi ciency among medical students

“…Cancer [7][8][9][10], multiple sclerosis [11] and autoimmune diseases [12], part from its traditional role in the bone health and reduction of bone fractures [13,14]. [15,16] and protects against Multiple Sclerosis, Epilepsy, Parkinson's disease, Autism and Schizophrenia [17].…”