AI Article Synopsis
- The study investigates the metabolic profiles in patients suspected of prostate cancer, focusing on differentiating clinically significant (csPCa) from clinically insignificant (ciPCa) and benign cases using serum samples.
- A 22-metabolite panel was identified, which improves the discrimination of csPCa when combined with traditional clinical parameters like age and PSA levels, achieving an AUC of 0.84.
- This research suggests that the identified metabolites, particularly ornithine and dimethylglycine, could serve as biomarkers to reduce unnecessary biopsies and identify potential treatment targets for prostate cancer.
Article Abstract
Context: Despite clinical suspicion of prostate cancer (PCa), 20-25% of patients exhibit a tumor-negative biopsy result.
Objective: To assess the serum metabolic profile of clinically significant (cs) compared to clinically insignificant (ci) PCa or benign (Be) patients.
Study Design: 1078 serum samples were analyzed.
Outcome Measurements And Statistical Analysis: Nuclear magnetic resonance (NMR) spectroscopy was used to quantify 73 metabolites, Random Forest for model algorithm.
Results: We identified a 22-metabolite panel, which discriminated csPCa (ISUP 2-5, n=328) from ciPCa (ISUP 1, n=101) and benign 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) (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 (TCA) cycle, cholesterol metabolism, and a significant increase of the inflammation marker GlycB 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<0.001) compared to Be+ciPCa patients (ornithine: 50.3 ± 31.6 µmol/l, dimethylglycine: 14.9 ± 7.7 µmol/l).
Conclusions: 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 supportive biomarker to reduce the number of unnecessary biopsies and also to identify novel therapeutic targets in the future.
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| http://dx.doi.org/10.1210/clinem/dgae704 | DOI Listing |
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