Prediction of clinically significant prostate cancer through urine metabolomic signatures: A large-scale validated study

Prediction of clinically significant prostate cancer through urine metabolomic signatures: A large-scale validated study

Abstract Purpose Currently, there are no accurate markers for predicting potentially lethal prostate cancer (PC) before biopsy. This study aimed to develop urine tests to predict clinically significant PC (sPC) in men at risk. Methods Urine samples from 928 men, namely, 660 PC patients and 268 benig...

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Published in:Journal of translational medicine 2023-10, Vol.21 (1), p.1-714, Article 714
Main Authors: Huang, Hsiang-Po, Chen, Chung-Hsin, Chang, Kai-Hsiung, Lee, Ming-Shyue, Lee, Cheng-Fan, Chao, Yen-Hsiang, Lu, Shih-Yu, Wu, Tzu-Fan, Liang, Sung-Tzu, Lin, Chih-Yu, Lin, Yuan Chi, Liu, Shih-Ping, Lu, Yu-Chuan, Shun, Chia-Tung, Huang, William J, Lin, Tzu-Ping, Ku, Ming-Hsuan, Chung, Hsiao-Jen, Chang, Yen-Hwa, Liao, Chun-Hou, Yu, Chih-Chin, Chung, Shiu-Dong, Tsai, Yao-Chou, Wu, Chia-Chang, Chen, Kuan-Chou, Ho, Chen-Hsun, Hsiao, Pei-Wen, Pu, Yeong-Shiau
Format: Article
Language:eng
Subjects:
Active surveillance
Aggressive
Analysis
Biomarkers
Biopsy
Care and treatment
Chromatography
Clinical significance
Diagnosis
Enrollments
Gas chromatography
Liquid biopsy
Liquid chromatography
Medical prognosis
Metabolism
Metabolites
Metabolomics
Metastasis
Mortality
Patients
Prediction
Prediction models
Prognosis
Prostate cancer
Prostate-specific antigen
Risk factors
Spectrophotometry
Urine
Urogenital system
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Summary:Abstract Purpose Currently, there are no accurate markers for predicting potentially lethal prostate cancer (PC) before biopsy. This study aimed to develop urine tests to predict clinically significant PC (sPC) in men at risk. Methods Urine samples from 928 men, namely, 660 PC patients and 268 benign subjects, were analyzed by gas chromatography/quadrupole time-of-flight mass spectrophotometry (GC/Q-TOF MS) metabolomic profiling to construct four predictive models. Model I discriminated between PC and benign cases. Models II, III, and GS, respectively, predicted sPC in those classified as having favorable intermediate risk or higher, unfavorable intermediate risk or higher (according to the National Comprehensive Cancer Network risk groupings), and a Gleason sum (GS) of ≥ 7. Multivariable logistic regression was used to evaluate the area under the receiver operating characteristic curves (AUC). Results In Models I, II, III, and GS, the best AUCs (0.94, 0.85, 0.82, and 0.80, respectively; training cohort, N = 603) involved 26, 24, 26, and 22 metabolites, respectively. The addition of five clinical risk factors (serum prostate-specific antigen, patient age, previous negative biopsy, digital rectal examination, and family history) significantly improved the AUCs of the models (0.95, 0.92, 0.92, and 0.87, respectively). At 90% sensitivity, 48%, 47%, 50%, and 36% of unnecessary biopsies could be avoided. These models were successfully validated against an independent validation cohort (N = 325). Decision curve analysis showed a significant clinical net benefit with each combined model at low threshold probabilities. Models II and III were more robust and clinically relevant than Model GS. Conclusion This urine test, which combines urine metabolic markers and clinical factors, may be used to predict sPC and thereby inform the necessity of biopsy in men with an elevated PC risk.
ISSN:1479-5876
1479-5876