Human Prostate-Specific Antigen Carries N-Glycans with Ketodeoxynononic Acid
Wei Wang,
Tao Zhang,
Jan Nouta,
Peter A. van Veelen,
Noortje de Haan,
Theo M. de Reijke,
Manfred Wuhrer,
Guinevere S.M. Lageveen-Kammeijer
Affiliations
Wei Wang
Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden 2333 ZA, Netherlands
Tao Zhang
Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden 2333 ZA, Netherlands
Jan Nouta
Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden 2333 ZA, Netherlands
Peter A. van Veelen
Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden 2333 ZA, Netherlands
Noortje de Haan
Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden 2333 ZA, Netherlands; Copenhagen Center for Glycomics, Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen DK-2200, Denmark
Theo M. de Reijke
Department of Urology, Amsterdam University Medical Centers, Location Academic Medical Center, University of Amsterdam, Amsterdam 1105 AZ, Netherlands
Manfred Wuhrer
Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden 2333 ZA, Netherlands
Guinevere S.M. Lageveen-Kammeijer
Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden 2333 ZA, Netherlands; Analytical Biochemistry, Groningen Research Institute of Pharmacy, Faculty of Science and Engineering, University of Groningen, Groningen 9747 AG, Netherlands; Corresponding author.
Ketodeoxynononic acid (Kdn) is a rather uncommon class of sialic acid in mammals. However, associations have been found between elevated concentrations of free or conjugated Kdn in relation to human cancer progression. Hitherto, there has been a lack of conclusive evidence that Kdn occurs on (specific) human glycoproteins (conjugated Kdn). Here, we report for the first time that Kdn is expressed on prostate-specific antigen (PSA) N-linked glycans derived from human seminal plasma and urine. Interestingly, Kdn was found only in an α2,3-linkage configuration on an antennary galactose, indicating a highly specific biosynthesis. This unusual glycosylation feature was also identified in a urinary PSA cohort in relation to prostate cancer (PCa), although no differences were found between PCa and non-PCa patients. Further research is needed to investigate the occurrence, biosynthesis, biological role, and biomarker potential of both free and conjugated Kdn in humans.
