Urinary marker panels for aggressive prostate cancer detection

Abstract Majority of patients with indolent prostate cancer (PCa) can be managed with active surveillance. Therefore, finding biomarkers for classifying patients between indolent and aggressive PCa is essential. In this study, we investigated urinary marker panels composed of urinary glycopeptides a...

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Main Authors: Tung-Shing Mamie Lih, Mingming Dong, Leslie Mangold, Alan Partin, Hui Zhang
Format: Article
Language:English
Published: Nature Portfolio 2022-09-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-022-19134-3
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author Tung-Shing Mamie Lih
Mingming Dong
Leslie Mangold
Alan Partin
Hui Zhang
author_facet Tung-Shing Mamie Lih
Mingming Dong
Leslie Mangold
Alan Partin
Hui Zhang
author_sort Tung-Shing Mamie Lih
collection DOAJ
description Abstract Majority of patients with indolent prostate cancer (PCa) can be managed with active surveillance. Therefore, finding biomarkers for classifying patients between indolent and aggressive PCa is essential. In this study, we investigated urinary marker panels composed of urinary glycopeptides and/or urinary prostate-specific antigen (PSA) for their clinical utility in distinguishing non-aggressive (Grade Group 1) from aggressive (Grade Group ≥ 2) PCa. Urinary glycopeptides acquired via data-independent acquisition mass spectrometry (DIA-MS) were quantitatively analyzed, where prostatic acid phosphatase (ACPP), clusterin (CLU), alpha-1-acid glycoprotein 1 (ORM1), and CD antigen 97 (CD97) were selected to be evaluated in various combinations with and without urinary PSA. Targeted parallel reaction monitoring (PRM) assays of the glycopeptides from urinary ACPP and CLU were investigated along with urinary PSA for the ability of aggressive PCa detection. The multi-urinary marker panels, combined via logistic regression, were statistically evaluated using bootstrap resampling and validated by an independent cohort. Majority of the multi-urinary marker panels (e.g., a panel consisted of ACPP, CLU, and Urinary PSA) achieved area under the curve (AUC) ranged from 0.70 to 0.85. Thus, multi-marker panels investigated in this study showed clinically meaningful results on aggressive PCa detection to separate Grade Group 1 from Grade Group 2 and above warranting further evaluation in clinical setting in future.
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spelling doaj.art-40a2ca5dadad4a44bb37f99f823dc30e2022-12-22T04:05:16ZengNature PortfolioScientific Reports2045-23222022-09-011211910.1038/s41598-022-19134-3Urinary marker panels for aggressive prostate cancer detectionTung-Shing Mamie Lih0Mingming Dong1Leslie Mangold2Alan Partin3Hui Zhang4Department of Pathology, School of Medicine, Johns Hopkins UniversityDepartment of Pathology, School of Medicine, Johns Hopkins UniversityThe Brady Urological Institute, The Johns Hopkins School of MedicineThe Brady Urological Institute, The Johns Hopkins School of MedicineDepartment of Pathology, School of Medicine, Johns Hopkins UniversityAbstract Majority of patients with indolent prostate cancer (PCa) can be managed with active surveillance. Therefore, finding biomarkers for classifying patients between indolent and aggressive PCa is essential. In this study, we investigated urinary marker panels composed of urinary glycopeptides and/or urinary prostate-specific antigen (PSA) for their clinical utility in distinguishing non-aggressive (Grade Group 1) from aggressive (Grade Group ≥ 2) PCa. Urinary glycopeptides acquired via data-independent acquisition mass spectrometry (DIA-MS) were quantitatively analyzed, where prostatic acid phosphatase (ACPP), clusterin (CLU), alpha-1-acid glycoprotein 1 (ORM1), and CD antigen 97 (CD97) were selected to be evaluated in various combinations with and without urinary PSA. Targeted parallel reaction monitoring (PRM) assays of the glycopeptides from urinary ACPP and CLU were investigated along with urinary PSA for the ability of aggressive PCa detection. The multi-urinary marker panels, combined via logistic regression, were statistically evaluated using bootstrap resampling and validated by an independent cohort. Majority of the multi-urinary marker panels (e.g., a panel consisted of ACPP, CLU, and Urinary PSA) achieved area under the curve (AUC) ranged from 0.70 to 0.85. Thus, multi-marker panels investigated in this study showed clinically meaningful results on aggressive PCa detection to separate Grade Group 1 from Grade Group 2 and above warranting further evaluation in clinical setting in future.https://doi.org/10.1038/s41598-022-19134-3
spellingShingle Tung-Shing Mamie Lih
Mingming Dong
Leslie Mangold
Alan Partin
Hui Zhang
Urinary marker panels for aggressive prostate cancer detection
Scientific Reports
title Urinary marker panels for aggressive prostate cancer detection
title_full Urinary marker panels for aggressive prostate cancer detection
title_fullStr Urinary marker panels for aggressive prostate cancer detection
title_full_unstemmed Urinary marker panels for aggressive prostate cancer detection
title_short Urinary marker panels for aggressive prostate cancer detection
title_sort urinary marker panels for aggressive prostate cancer detection
url https://doi.org/10.1038/s41598-022-19134-3
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