Targeted Mass Spectrometry Assays for Specific Quantification of Urinary proPSA Isoforms
| Autor: | 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 |
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| Rok vydání: | 2023 |
| Předmět: | |
| Zdroj: | J Proteome Res |
| ISSN: | 1535-3907 1535-3893 |
| DOI: | 10.1021/acs.jproteome.2c00745 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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