Targeted Mass Spectrometry Assays for Specific Quantification of Urinary proPSA Isoforms

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

Producción científica: Articlerevisión exhaustiva

1 Cita (Scopus)


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.

Idioma originalEnglish (US)
Páginas (desde-hasta)942-950
Número de páginas9
PublicaciónJournal of Proteome Research
EstadoPublished - mar 3 2023

ASJC Scopus subject areas

  • General Chemistry
  • Biochemistry


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