Reduced Uncoupling Protein 1 Expression in Periprostatic Adipose Tissue and Its Association With Higher Prostate Cancer Grade

Background Periprostatic adipose tissue (PPAT) is increasingly recognized as a component of the prostate cancer (PCa) microenvironment. However, the role of uncoupling protein 1 (UCP1) in PPAT remains unclear. We investigated the association between PCa grade and UCP1 expression in PPAT. Methods After institutional review board approval, we collected PPAT and abdominopelvic adipose tissue (APAT) samples from 83 Japanese patients who underwent robot‐assisted radical prostatectomy for clinically localized PCa. UCP1 mRNA expression in PPAT was quantified by RT‐qPCR and normalized to APAT expression (PPAT/APAT ratio). PPAT volume was estimated by computed tomography. Associations with pathological stage and International Society of Urological Pathology (ISUP) grade were evaluated, and logistic regression was performed to identify factors associated with high‐grade disease (ISUP 4/5). Results In the univariable logistic regression analysis, lower (log‐transformed) UCP1 expression was significantly associated with high‐grade PCa ( ISUP 4/5) (odds ratio [ OR ] 0.415, 95% confidence interval [ CI ] 0.180–0.883, p = 0.027). Age, prostate serum antigen ( PSA ) concentration, and PPAT volume were not significantly associated with high‐grade disease. In the multivariable analysis adjusted for age, PSA concentration, and PPAT volume, UCP1 expression remained independently associated with high‐grade PCa ( OR 0.438, 95% CI 0.188–0.945, p = 0.035). No other clinicopathological variables demonstrated independent associations. Conclusions Reduced UCP1 expression in PPAT was independently associated with high‐grade PCa. PPAT UCP1 expression may represent a microenvironment‐associated marker reflecting PCa severity.