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Metabolites
Volume 15
Issue 12
10.3390/metabo15120757
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Evaluating Differential Metabolic Profiles by Prostate Cancer Risk Among Prostate Cancer Patients

by
Tuo Liu
1,
Jahnvi Roorkeewal
2,
Melissa A. Furlong
1,
Shawn C. Beitel
1,
Jefferey L. Burgess
1,
Benjamin R. Lee
3,
Juan Chipollini
3,
Justin M. Snider
2,* and
Ken Batai
4,*
1
Department of Community, Environment, and Policy, Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, AZ 85724, USA
2
School of Nutritional Sciences and Wellness, University of Arizona, Tucson, AZ 85721, USA
3
Department of Urology, College of Medicine-Tucson, University of Arizona, Tucson, AZ 85724, USA
4
Department of Cancer Prevention & Control, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14203, USA
*
Authors to whom correspondence should be addressed.
Metabolites 2025, 15(12), 757; https://doi.org/10.3390/metabo15120757
Submission received: 14 September 2025 / Revised: 17 November 2025 / Accepted: 19 November 2025 / Published: 21 November 2025
(This article belongs to the Section Endocrinology and Clinical Metabolic Research)
Versions Notes

Abstract

Background: Currently there are no clinically validated biomarkers recommended for prostate cancer (PCa) risk stratification other than prostate-specific antigen (PSA). Objective: This study aimed to identify urine metabolites that are associated with the presence of high-grade PCa at the time of radical prostatectomy. Methods: Urine samples were collected from patients who underwent radical prostatectomy. High-resolution metabolomics were implemented using liquid chromatography mass spectrometry (LC-MS). To enhance metabolic feature identification, sample extracts were analyzed in two modes, C18 chromatography [reverse-phase (RP)] and hydrophilic interaction chromatography (HILIC). Results: This analysis included a total of 22 patients with PCa (10 high-grade and 12 low-grade) and identified 52 differential metabolites, 40 in RP and 12 in HILIC, at the p-value 0.05 level. Among these, methyl alpha-aspartyl phenylalaninate was most significantly differentiated, while 3-methylbutanoicacid had the largest difference (slope −3.488). In the pathway analysis, the histidine metabolism pathway was significantly enriched (p < 0.05) with an enrichment factor of 3.5. Although not statistically significant, alterations were also observed in the vitamin B12, B7 (biotin), B6, and B3 (niacin) pathways. Conclusions: These findings suggest that urinary metabolites may have the potential to differentiate high-grade from low-grade PCa. Our study also highlights the metabolic reprogramming that occurs as PCa becomes more aggressive and potential differences in dietary patterns.
Keywords: prostate cancer (PCa); urine metabolomics; PCa risk prostate cancer (PCa); urine metabolomics; PCa risk

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MDPI and ACS Style

Liu, T.; Roorkeewal, J.; Furlong, M.A.; Beitel, S.C.; Burgess, J.L.; Lee, B.R.; Chipollini, J.; Snider, J.M.; Batai, K. Evaluating Differential Metabolic Profiles by Prostate Cancer Risk Among Prostate Cancer Patients. Metabolites 2025, 15, 757. https://doi.org/10.3390/metabo15120757

AMA Style

Liu T, Roorkeewal J, Furlong MA, Beitel SC, Burgess JL, Lee BR, Chipollini J, Snider JM, Batai K. Evaluating Differential Metabolic Profiles by Prostate Cancer Risk Among Prostate Cancer Patients. Metabolites. 2025; 15(12):757. https://doi.org/10.3390/metabo15120757

Chicago/Turabian Style

Liu, Tuo, Jahnvi Roorkeewal, Melissa A. Furlong, Shawn C. Beitel, Jefferey L. Burgess, Benjamin R. Lee, Juan Chipollini, Justin M. Snider, and Ken Batai. 2025. "Evaluating Differential Metabolic Profiles by Prostate Cancer Risk Among Prostate Cancer Patients" Metabolites 15, no. 12: 757. https://doi.org/10.3390/metabo15120757

APA Style

Liu, T., Roorkeewal, J., Furlong, M. A., Beitel, S. C., Burgess, J. L., Lee, B. R., Chipollini, J., Snider, J. M., & Batai, K. (2025). Evaluating Differential Metabolic Profiles by Prostate Cancer Risk Among Prostate Cancer Patients. Metabolites, 15(12), 757. https://doi.org/10.3390/metabo15120757

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