Identification of Differential Patterns of Oxidative Biomarkers in Prostate Cancer Progression

INTRODUCTION:Oxidative stress has been found to be associated with the progression of prostate cancer (PCa); however, human studies which identify differential roles of each oxidation pathway in PCa progression are lacking. We aimed to identify which oxidative stress markers, specifically lipid and global oxidation and glycation, are associated with PCa progression. PATIENTS AND METHODS:We recruited 3 groups of patients from a urologic clinic at the University of Cincinnati Medical Center: men with PCa who had undergone prostatectomy, men with PCa under watchful waiting, and men with benign prostatic hyperplasia (BPH). We used the most commonly used lipid oxidation marker, F2-isoprostanes; global oxidation markers, fluorescent oxidation products (FlOPs); and the commonly used marker for advanced glycation end products, carboxymethyllysine. These biomarkers were measured in plasma samples at baseline entry. Plasma prostate-specific antigen (PSA) was measured at enrollment and follow-up visits. RESULTS:Compared with men with BPH, men with PCa who had undergone prostatectomy had 26% (P = .01) higher levels of F2-isoprostanes and 20% (P = .08) higher levels of carboxymethyllysine. All the oxidation markers were similar when comparing men under watchful waiting with men with BPH. When examining the associations between baseline oxidation markers and follow-up PSAs, we found that different oxidation markers had differential patterns associated with PSA elevation. F2-isoprostanes were positively associated with PSA elevation among men with PCa; FlOP_320 was positively associated with PSA elevation among both men with PCa and men with BPH, whereas among men with PCa under watchful waiting, FlOP_360 and FlOP_400 had opposite trends of associations with PSA elevation. CONCLUSIONS:Our study suggested that high levels of lipid oxidation were associated with PCa progression, whereas different global oxidation markers had different patterns associated with PCa progression. Large-scale clinical studies are needed to confirm our associations. Our study provides a comprehensive view of the relationship between biomarkers and PCa progression.