Details

Autor(en) / Beteiligte

• Kitata, Reta Birhanu
• Hu, Lisa Y.
• Lin, Tai-Tu
• Nicora, Carrie D.
• Fillmore, Thomas L.
• Nie, Song
• Hudson, Robert D.
• Liu, Tao
• Leach, Robin J.
• Liu, Alvin Y.
• Qian, Wei-Jun
• Shi, Tujin

Titel

Targeted Mass Spectrometry Assays for Specific Quantification of Urinary proPSA Isoforms

Ist Teil von

• Journal of proteome research, 2023-03, Vol.22 (3), p.942-950

Ort / Verlag

United States: American Chemical Society

Erscheinungsjahr

2023

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.