Expression of Vitamin D Receptor (VDR) Positively Correlates with Survival of Urothelial Bladder Cancer Patients.
Expression of Vitamin D Receptor (VDR) Positively Correlates with Survival of Urothelial Bladder Cancer Patients.
复制标题
维生素D受体（VDR）的表达与尿路上皮膀胱癌患者的存活正相关。
DOI：
10.3390/ijms161024369
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发表时间：
2015-10-15
影响因子：
5.6
通讯作者：
Slominski AT
中科院分区：
文献类型：
--
作者：
Jóźwicki W;Brożyna AA;Siekiera J;Slominski AT
维生素D3通过维生素D受体（VDR）发挥作用，显示出抑瘤和抗癌作用，而CYP 27 B1对25-羟基维生素D3 1α位的羟基化是其活化的重要步骤。VDR和CYP 27 B1在许多正常组织和肿瘤组织中均有表达，但其在膀胱癌中的表达尚不清楚。本研究的目的是探讨VDR和CYP 27 B1在膀胱癌中的表达是否与预后标志物和疾病结局相关。我们分析了71例膀胱癌患者的肿瘤和正常组织中的VDR和CYP 27 B1。在正常上皮中发现最高的VDR免疫染色，并且在膀胱癌细胞中显著较低（用Mann-Whitney U检验，p < 0.001）。VDR表达在更晚期（pT 2b-pT 4）（用Mann-Whitney U检验，p = 0.005）和转移性癌症（分别用核和细胞质VDR免疫染色的Mann-Whitney U检验，p < 0.05和p = 0.004）中最低。缺乏细胞质和细胞核VDR也与较短的总生存期相关（细胞质VDR免疫定位生存期为13.3个月vs. 55.3个月，HR = 1.92，p = 0.04，细胞核VDR免疫染色生存期为13.5个月vs. 55.3个月，HR = 2.47，p = 0.002，Mantel-Cox检验）。在缺乏高细胞质VDR染色的病例中，在较高百分比的肿瘤区域中观察到非经典分化（ND）。CYP 27 B1在癌细胞中的表达低于正常上皮细胞（Mann-Whitney U检验p = 0.03），但其表达与肿瘤分期（pT）、转移、分级、有丝分裂活性或总生存期无关。总之，VDR和CYP 27 B1的表达在尿路上皮膀胱癌中失调。虽然我们的研究结果显示VDR表达减少与预后标志物和生存时间之间的关系表明VDR作为预后不良的新指标的潜在有用性，但需要在不同患者队列中进行独立组的进一步研究以验证这一假设。我们还认为，维生素D为基础的治疗可能是一种辅助策略，在膀胱癌表达VDR的治疗。
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.