Clinicopathological correlates of vitamin D receptor expression in prostate cancer: results of genomic analysis

Abstract

Abstract Objectives: Prostate cancer (PCa) is the most common malignancy in men. Geography and environmental factors have been associated with varying incidence and mortalities in different groups. Vitamin D has antiproliferative effect on PCa cells, and its effect is mediated through vitamin D receptor (VDR). This study reported the correlation of VDR expression with some clinicopathological and biological features among a cohort of patients with PCa. Methods: Genomic and clinicopathological data of 497 patients with PCa reposited in The Cancer Genome Atlas were retrieved using Linux command in running codes and scripts and extrapolated onto SPSS version 28 for statistical analysis. Descriptive and inferential statistics were conducted to determine the proportions and associations of VDR expression with genomic variables and clinicopathological indices. The mechanism of VDR dysregulation was also interrogated. Results: Our results showed that high VDR expression was positively correlated with a high Gleason score ( P < 0.001), poorer prognostic International Society of Urological Pathology grade groups ( P < 0.001), advanced tumor stage ( P = 0.01), and poorer response to androgen deprivation therapy (ADT). Age, race, and overall and disease-free survival did not show any correlation with VDR expression ( P > 0.05). Furthermore, the major mechanism of dysregulation of VDR in PCa was by aberrant methylation of the VDR promoter region ( P < 0.001), and not by copy number alterations ( P = 0.42). Conclusion: VDR expression is associated with adverse clinicopathological indices, including late-stage disease profile, high-grade indices, and poorer response to ADT. VDR is also mainly deregulated by aberrant epigenetic mechanism. The study is limited by absence of some clinical information such as sunlight exposure.