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Targeted Mass Spectrometry Assays for Specific Quantification of Urinary proPSA Isoforms.

ABSTRACT: Prostate cancer (PCa) is the second leading cause of male cancer-related deaths in the United States. The pre-mature forms of prostate-specific antigen (PSA), proPSA, were shown to be associated with PCa. However, there is a technical challenge in the development of antibody-based immunoassays for specific recognition of each individual proPSA isoform. Herein, we report the development of highly specific, antibody-free, targeted mass spectrometry assays for simultaneous quantification of [-2], [-4], [-5], and [-7] proPSA isoforms in voided urine. The newly developed proPSA assays capitalize on Lys-C digestion to generate surrogate peptides with appropriate length (9-16 amino acids) along with long-gradient liquid chromatography separation. The assay utility of these isoform markers was evaluated in a cohort of 30 well-established clinical urine samples for distinguishing PCa patients from healthy controls. Under the 95% confidence interval, the combination of [-2] and [-4] proPSA isoforms yields the area under curve (AUC) of 0.86, and the AUC value for the combined all four isoforms was calculated to be 0.85. We have further verified [-2]proPSA, the dominant isoform, in an independent cohort of 34 clinical urine samples. Validation of proPSA isoforms in large-scale cohorts is needed to demonstrate their potential clinical utility.

SUBMITTER: Kitata RB

PROVIDER: S-EPMC10072162 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Targeted Mass Spectrometry Assays for Specific Quantification of Urinary proPSA Isoforms.

Kitata Reta Birhanu RB Hu Lisa Y LY Lin Tai-Tu TT Nicora Carrie D CD Fillmore Thomas L TL Nie Song S Hudson Robert D RD Liu Tao T Leach Robin J RJ Liu Alvin Y AY Qian Wei-Jun WJ Shi Tujin T

Journal of proteome research 20230110 3

Prostate cancer (PCa) is the second leading cause of male cancer-related deaths in the United States. The pre-mature forms of prostate-specific antigen (PSA), proPSA, were shown to be associated with PCa. However, there is a technical challenge in the development of antibody-based immunoassays for specific recognition of each individual proPSA isoform. Herein, we report the development of highly specific, antibody-free, targeted mass spectrometry assays for simultaneous quantification of [-2], [ ...[more]

PMID: 36626706

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Dataset Information

Targeted Mass Spectrometry Assays for Specific Quantification of Urinary proPSA Isoforms.

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Targeted Mass Spectrometry Assays for Specific Quantification of Urinary proPSA Isoforms.

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