Oligosaccharide profiles of the prostate specific antigen in free and complexed forms from the prostate cancer patient serum and in seminal plasma: a glycopeptide approach.
The oligosaccharide structures of prostate specific antigen (PSA) are expected to be useful in discriminating prostate cancer from benign conditions both accompanied by increased serum PSA levels. A large proportion of PSA forms a covalent complex with a glycoprotein, alpha(1)-antichymotrypsin, in human blood. In the present study, the glycan profiles of free and complexed forms of PSA from cancer patient serum and of seminal plasma PSA were compared by analyzing the glycopeptides obtained by lysylendopeptidase digestion of the electrophoretically separated PSA with mass spectrometry. The profiles of the PSA N-glycans from the free and complexed molecules were quite similar to each other and consisted of fucosylated biantennary oligosaccharides as the major class. They were mostly sialylated, and a considerable sialic acid fraction was alpha2,3-linked as determined by Streptococcus pneumoniae neuraminidase digestion of the glycopeptides. In the seminal plasma PSA, high-mannose and hybrid types of oligosaccharides were predominant, and the sialic acids attached to the latter as well as to biantennary oligosaccahrides were exclusively alpha2,6-linked because they were removed by Arthrobacter ureafaciens neuraminidase but resistant to S. pneumoniae neuraminidase. Complex-type oligosaccharides from other sources were found in the seminal plasma sample, indicating that analysis of released glycans carries a risk of being misleading. The results suggest that identification of alpha2,3-linked sialic acids on PSA potentially discriminates malignant from benign conditions, if the analysis is applied to oligosaccharides specifically attached to the N-glycosylation site of PSA in either a free or a complexed form in the serum.
Tajiri
Michiko
M
Department of Molecular Medicine, Osaka Medical Center and Research Institute for Maternal and Child Health, 840 Murodo-cho Izumi, Osaka 594-1101, Japan.
Ohyama
Chikara
C
Wada
Yoshinao
Y
D000595:Amino Acid Sequence; D014408:Biomarkers, Tumor / Q000097:blood / Q000737:chemistry*; D045744:Cell Line, Tumor; D005643:Fucose / Q000032:analysis; D006020:Glycopeptides / Q000737:chemistry*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000097:blood / Q000737:chemistry*; D017430:Prostate-Specific Antigen / Q000097:blood / Q000737:chemistry* / Q000302:isolation & purification; D011471:Prostatic Neoplasms / Q000097:blood / Q000737:chemistry* / Q000175:diagnosis; D012661:Semen / Q000737:chemistry*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D014408:Biomarkers, Tumor; D006020:Glycopeptides; D009844:Oligosaccharides; D005643:Fucose; D017430:Prostate-Specific Antigen