FIGURE 6.

VDR cistrome-transciptome relationships in prostate cancer. A, A cohort of 7 AA patients with prostate cancer with conserved African genomic ancestry and 16 EA patients with prostate cancer were treated with vitamin D₃ (4,000 IU daily), and RNA-seq undertaken on the tumors following radical prostatectomy, as we reported previously (6). Significantly differentially regulated genes in the AA prostate cancer group (there were no DEGs in the EA prostate cancer group) were overlapped with genes annotated to ATAC-seq or ChIP-seq regions within 100 kb. The Volcano plot of the DEGs for the response in AA men (left), or comparing basal AA to EA prostate cancer (right) and annotated with genes that are VDR bound and/or 1α,25(OH)₂D₃-dependent NF region annotated genes. B, RNA-seq was undertaken in tumors from a cohort of 57 AA and 18 EA patients who underwent radical prostatectomy at Northwestern Medical Center. Tumor-specific significant DEGs were identified for deficient serum 25(OH)D₃ (serum 25(OH)D₃ levels < 12 ng/mL; low; left) or obesity (BMI > 30; O; right). In each case BMI or 25(OH)D₃ levels were kept as a continuous variable, respectively. The DEGs for 25(OH)D₃ deficiency (left) of obesity (right) in the AA prostate cancer group (there were no DEGs in the EA prostate cancer group) were overlapped with genes annotated to ATAC-seq or ChIP-seq regions within 100 kb. C, Partial correlation analyses in equal numbers of AA or EA tumors (n = 36) from Northwestern cohort was undertaken between VDR and either AA or EA ChIP-seq annotated genes in AA and EA tumors respectively considering the impact of the indicated coregulators. The change in the correlation (delta.corr) was calculated as the difference between the Pearson correlation and Pearson partial correlations between VDR and these target genes and each of the indicated coregulators.