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Development of Parallel Reaction Monitoring Assays for the Detection of Aggressive Prostate Cancer Using Urinary
Mingming Dong1, Tung-Shing Mamie Lih1, Naseruddin Höti1
1Department of Pathology, School of Medicine, Johns Hopkins University, 400 N. Broadway Street, Smith Building, Room 4011, Baltimore, Maryland 21231, United States.
Journal of Proteome Research
|June 9, 2021
Summary
New urinary glycopeptide assays for prostatic acid phosphatase (ACPP) and clusterin (CLU) show promise for detecting aggressive prostate cancer (PCa). Combined with serum prostate-specific antigen (PSA), these biomarkers improve PCa detection accuracy.
Area of Science:
- Biochemistry
- Oncology
- Proteomics
Background:
- Accurate detection of aggressive prostate cancer (PCa) is crucial for effective treatment.
- Existing biomarkers like serum prostate-specific antigen (PSA) have limitations in specificity and sensitivity.
- Urinary glycoproteins offer a potential alternative or adjunct for PCa diagnostics.
Purpose of the Study:
- To develop and validate robust targeted parallel reaction monitoring (PRM) assays for urinary prostatic acid phosphatase (ACPP) and clusterin (CLU) glycopeptides.
- To assess the diagnostic performance of these urinary biomarkers, individually and in combination with serum PSA, for aggressive PCa detection.
- To facilitate the clinical translation of novel glycoproteomic findings into practical diagnostic tests.
Main Methods:
- Development of targeted parallel reaction monitoring (PRM) assays for specific urinary glycopeptides from ACPP and CLU.
- Quantitative analysis of urinary samples from patients with nonaggressive (Gleason score = 6) and aggressive (Gleason ≥ 8) PCa.
- Assessment of diagnostic accuracy using area under the curve (AUC), sensitivity, and specificity.
Main Results:
- Developed PRM assays exhibited good repeatability and a wide working range.
- Combining urinary ACPP and CLU improved PCa discrimination (AUC from 0.66 to 0.78).
- A three-signature panel (urinary ACPP, CLU, and serum PSA) achieved an AUC of 0.83, outperforming serum PSA alone (AUC 0.68).
Conclusions:
- Validated PRM assays for urinary ACPP and CLU glycopeptides are effective for aggressive PCa detection.
- The combination of urinary ACPP, CLU, and serum PSA offers enhanced predictive power for aggressive PCa.
- These urinary glycopeptide assays show potential as a valuable adjunct to serum PSA testing for improved PCa diagnostics.
