CONTEXT: Despite clinical suspicion of prostate cancer (PCa), 20% to 25% of patients exhibit a tumor-negative biopsy result. OBJECTIVE: This work aimed to assess the serum metabolic profile of clinically significant (cs) compared to clinically insignificant (ci) PCa or benign (Be) patients. METHODS: A total of 1078 serum samples were analyzed. Nuclear magnetic resonance (NMR) spectroscopy was used to quantify 73 metabolites
random forest was used for the model algorithm. RESULTS: We identified a 22-metabolite panel, which discriminated csPCa (International Society of Urological Pathology [ISUP] 2-5, n = 328) from ciPCa (ISUP 1, n = 101) and Be patients (negative biopsy, n = 649) with a higher performance when combined with the standard clinical parameters age, prostate-specific antigen (PSA), and percentage free PSA (%fPSA) (area under the curve [AUC] 0.84) than the clinical parameters alone (AUC 0.73). Our study further revealed significant dysregulations of the urea cycle and the choline pathway along with changes in tricarboxylic acid cycle, cholesterol metabolism, and a significant increase of the inflammation marker glycoprotein acetyls B in csPCa patients. In particular, ornithine and dimethylglycine were the 2 most important features to discriminate csPCa from Be + ciPCa with significantly higher ornithine and lower dimethylglycine levels in patients with csPCa (ornithine: 63.7 ± 26.5 µmol/L, dimethylglycine: 12.6 ± 6.3 µmol/L
P <
.002) compared to Be + ciPCa patients (ornithine: 50.3 ± 31.6 µmol/L, dimethylglycine: 14.9 ± 7.7 µmol/L). CONCLUSION: This study discovered a 22-metabolite panel to discriminate patients with csPCa from Be + ciPCa patients when combined with age, PSA, and %fPSA. It may therefore be used as a supportive biomarker to reduce the number of unnecessary biopsies and also to identify novel therapeutic targets in the future.