Expression of Vitamin D Receptor (VDR) Positively Correlates with Survival of Urothelial Bladder Cancer Patients
Abstract
:1. Introduction
2. Results
2.1. VDR and Bladder Cancer
VDR Expression | Total Cases (n) | Deaths (n) | Median Overall Survival (Months) | Log-Rank (Mantel–Cox) Test | Gehan–Breslow–Wilcoxon Test | Hazard Ratio (95% CI) | |
---|---|---|---|---|---|---|---|
χ2 (p Value) | χ2 (p Value) | ||||||
Nuclear VDR | Absent | 9 | 8 | 13.3 | 5.60 (0.02) | 4.00 (<0.05) | 2.47 |
Present | 62 | 30 | 55.3 | (0.85–7.22) | |||
Cytoplasmic VDR | Absent | 22 | 15 | 13.5 | 4.07 (0.04) | 4.63 (0.03) | 1.92 |
Present | 49 | 23 | 55.3 | (0.53–4.00) | |||
Either nuclear or cytoplasmic VDR | Absent | 9 | 8 | 13.5 | 5.63 (0.02) | 4.00 (<0.05) | 2.47 |
Present | 62 | 30 | 55.3 | (0.85–7.22) |
Adjustment | χ2 | p Value | Variable | b | SE | p Value | Exp(b) | 95% CI | |
---|---|---|---|---|---|---|---|---|---|
Nuclear VDR | |||||||||
Age and gender | 9.45 | 0.024 | Nuclear VDR | −0.85 | 0.40 | 0.04 | 0.43 | 0.20–0.94 | |
Age | 0.04 | 0.02 | 0.03 | 1.05 | 1.01–1.09 | ||||
Gender * | 0.10 | 0.43 | 0.81 | 1.10 | 0.48–2.56 | ||||
Age, gender and advancement | 17.13 | 0.002 | Nuclear VDR | −1.10 | 0.41 | 0.01 | 0.34 | 0.15–0.75 | |
Age | 0.04 | 0.02 | 0.04 | 1.05 | 1.00–1.09 | ||||
Gender * | 0.10 | 0.43 | 0.81 | 1.10 | 0.48–2.56 | ||||
Advancement ** | 1.12 | 0.45 | 0.01 | 3.09 | 1.27–7.49 | ||||
Age, gender and metastases | 14.24 | 0.01 | Nuclear VDR | −0.56 | 0.47 | 0.23 | 0.60 | 0.23–1.42 | |
Age | 0.05 | 0.02 | 0.03 | 1.05 | 1.00–1.10 | ||||
Gender * | −0.27 | 0.49 | 0.58 | 0.76 | 0.30–2.00 | ||||
Metastases *** | 0.98 | 0.37 | 0.01 | 2.67 | 1.29–5.51 | ||||
Age, gender, advancement, the presence of metastases | 17.22 | 0.004 | Nuclear VDR | −0.79 | 0.50 | 0.11 | 0.45 | 0.17–1.17 | |
Age | 0.05 | 0.02 | 0.04 | 1.05 | 1.00–1.10 | ||||
Gender * | −0.12 | 0.50 | 0.81 | 0.89 | 0.34–2.32 | ||||
Advancement ** | 0.81 | 0.49 | 0.10 | 2.24 | 0.86–5.87 | ||||
Metastasis *** | 0.68 | 0.40 | 0.09 | 1.97 | 0.89–4.33 | ||||
Cytoplasmic VDR | |||||||||
Age and gender | 9.95 | 0.02 | Cytoplasmic VDR | −0.72 | 0.34 | 0.03 | 0.49 | 0.25–0.94 | |
Age | 0.05 | 0.02 | 0.02 | 1.05 | 1.01–1.09 | ||||
Gender * | 0.10 | 0.43 | 0.81 | 1.11 | 0.48–2.58 | ||||
Age, gender and advancement | 15.98 | 0.003 | Cytoplasmic VDR | −0.75 | 0.34 | 0.03 | 0.47 | 0.24–0.92 | |
Age | 0.05 | 0.02 | 0.03 | 1.05 | 1.00–1.09 | ||||
Gender * | 0.16 | 0.43 | 0.71 | 1.17 | 0.50–2.73 | ||||
Advancement ** | 0.99 | 0.45 | 0.03 | 2.70 | 1.13–6.46 | ||||
Age, gender and metastases | 17.13 | 0.002 | Cytoplasmic VDR | −0.43 | 0.37 | 0.25 | 0.65 | 0.32–1.34 | |
Age | 0.05 | 0.02 | 0.02 | 1.05 | 1.01–1.10 | ||||
Gender * | −0.26 | 0.49 | 0.59 | 0.77 | 0.30–2.00 | ||||
Metastases *** | 0.91 | 0.38 | 0.02 | 2.50 | 1.18–5.26 | ||||
Age, gender, advancement, the presence of metastases | 16.72 | 0.005 | Cytoplasmic VDR | −0.52 | 0.38 | 0.17 | 0.59 | 0.28–1.25 | |
Age | 0.05 | 0.02 | 0.04 | 1.05 | 1.00–1.10 | ||||
Gender * | −0.11 | 0.50 | 0.82 | 0.89 | 0.34–2.36 | ||||
Advancement ** | 0.72 | 0.48 | 0.13 | 2.05 | 0.81–5.22 | ||||
Metastasis *** | 0.66 | 0.40 | 0.10 | 1.94 | 0.89–4.26 |
2.2. CYP2B1 and Bladder Cancer
Feature | Nuclear VDR | Cytoplasmic VDR | CYP27B1 | ||||
---|---|---|---|---|---|---|---|
Mean (AU) | p Value | Mean (AU) | p Value | Mean (AU) | p Value | ||
Normal epithelium | 1.3 | <0.001 * | 1.0 | 0.2 * | 2.0 | 0.03 * | |
Normal epithelium near tumor | 1.2 | 0.01 * | 1.1 | 0.5 * | 1.9 | 0.1 * | |
Tumor | 0.9 | – | 1.1 | 1.6 | – | ||
pT | pTa-pT2a | 0.8 | 0.3 | 1.4 | 0.005 | 1.6 | 0.06 |
pT2b-pT4 | 0.7 | 1.0 | 1.8 | ||||
Metastasis | absent | 1.0 | <0.05 | 1.1 | <0.05 | 1.6 | 0.1 |
present | 0.8 | 0.9 | 1.8 | ||||
Tumor grade | high | 0.9 | 0.3 | 0.8 | 0.2 | 1.7 | 0.07 |
low | 0.9 | 1.0 | 1.5 | ||||
Mitosis | <10 mitoses per 1000 tumor cells | 1.1 | 0.08 | 1.0 | 0.2 | 1.5 | 0.2 |
>10 mitoses per 1000 tumor cells | 0.9 | 0.8 | 1.7 |
3. Discussion
4. Experimental Section
4.1. Patients and Pathological Morphological Assessment
Feature | Number of Patients | |
---|---|---|
Gender | female | 13 |
males | 58 | |
pT a | a | 5 |
is | 1 | |
1 | 12 | |
2a | 3 | |
2b | 14 | |
3 | 24 | |
4 | 12 | |
NDs b | Absent | 32 |
Present | 39 | |
Grade | Low grade | 19 |
High grade | 52 | |
Metastases | Absent | 44 |
Present | 27 | |
Second tumor | Absent | 62 |
Present | 9 | |
Concomitant carcinoma in situ | Absent | 64 |
Present | 7 | |
Survival | Alive | 33 |
Death | 38 |
4.2. Immunohistochemical Staining and Evaluation of the VDR
4.3. Evaluation of the NDs
4.4. Statistical Analyses
5. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
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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. https://doi.org/10.3390/ijms161024369
Jóźwicki W, Brożyna AA, Siekiera J, Slominski AT. Expression of Vitamin D Receptor (VDR) Positively Correlates with Survival of Urothelial Bladder Cancer Patients. International Journal of Molecular Sciences. 2015; 16(10):24369-24386. https://doi.org/10.3390/ijms161024369
Chicago/Turabian StyleJóźwicki, Wojciech, Anna A. Brożyna, Jerzy Siekiera, and Andrzej T. Slominski. 2015. "Expression of Vitamin D Receptor (VDR) Positively Correlates with Survival of Urothelial Bladder Cancer Patients" International Journal of Molecular Sciences 16, no. 10: 24369-24386. https://doi.org/10.3390/ijms161024369