The Association Between CYP7B1 and Diabetes in Prostate Cancer patients (DIAMOND study)

Abstract Background: Prostate cancer (PCa) is the second most frequently diagnosed cancer in men, and the extent of CYP7B1's involvement in androgen metabolism and its impact on the progression of PCa is still uncertain. The aim of this study is to investigate the role of the CYP7B1 enzyme in prostate cancer aggressiveness. Methods: A retrospective analysis was performed on 390 patients with prostate cancer (PCa) or benign prostatic hyperplasia (BPH) at the Department of Urology, University of Catania, where we examined CYP7B1 protein expression through immunohistochemical analysis in malignant and benign prostatic tissue. We investigated the interactions between CYP7B1 expression and proteins associated with PCa and metabolic processes, followed by an analysis of the risk of biochemical recurrence based on CYP7B1 expression. Results: Among 286 patients with PCa and 104 patients with BPH, CYP7B1 expression was higher in malignant tissue. Of the 139 patients with elevated CYP7B1 expression, 92.8% had prostate cancer. Logistic regression revealed significantly higher positive scores for IR-α (OR 5.73, CI: 2.77-11.84, p < 0.01), IR-β (OR 6.61, CI: 2.19-19.96, p < 0.01), SRSF-1 (OR 2.04, CI: 1.27-3.29, p < 0.01), FAS (OR 2.15, CI: 1.28-3.62, p < 0.01), PSMA (OR 1.66, CI: 1.04-2.66, p = 0.03), and ACC-1 (OR 1.83, CI: 1.14-2.93, p = 0.01). Overall, no increased risk of biochemical recurrence was associated with CYP7B1 expression. However, in a non-diabetic subgroup analysis, higher CYP7B1 expression indicated a higher risk of biochemical recurrence with HR of 1.78 (CI: 1.0-3.2, p = 0.05). Conclusion: PCa is associated with elevated CYP7B1 expression. In a subgroup of non-diabetic patients, elevated CYP7B1 expression was associated with increased risk of biochemical recurrence, suggesting increased cancer aggressiveness.