title: Simultaneous analysis of glycosylated and sialylated prostate-specific antigen revealing differential distribution of glycosylated prostate-specific antigen isoforms in prostate cancer tissues.
abstract: Aberrant protein glycosylation has been shown to be associated with disease progression and can be potentially useful as a biomarker if disease-specific glycosylation can be identified. However, high-throughput quantitative analysis of protein glycosylation derived from clinical specimens presents technical challenges due to the typically high complexity of biological samples. In this study, a mass spectrometry-based analytical method was developed to measure different glycosylated forms of glycoproteins from complex biological samples by coupling glycopeptide extraction strategy for specific glycosylation with selected reaction monitoring (SRM). Using this method, we monitored glycosylated and sialylated prostate-specific antigen (PSA) in prostate cancer and noncancer tissues. Results of this study demonstrated that the relative abundance of glycosylated PSA isoforms were not correlated with total PSA protein levels measured in the same prostate cancer tissue samples by clinical immunoassay. Furthermore, the sialylated PSA was differentially distributed in cancer and noncancer tissues. These data suggest that differently glycosylated isoforms of glycoproteins can be quantitatively analyzed and may provide unique information for clinically relevant studies.
authors.affiliation: Department of Pathology, Johns Hopkins University, Baltimore, Maryland 21287, United States.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Yuan
authors.initials: Y
authors.lastname: Tian
authors.forename: Taha
authors.initials: T
authors.lastname: Rezai
authors.forename: Amol
authors.initials: A
authors.lastname: Prakash
authors.forename: Mary F
authors.initials: MF
authors.lastname: Lopez
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Chan
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
mesh_terms: D014408:Biomarkers, Tumor / Q000737:chemistry / Q000378:metabolism; D005260:Female; D006020:Glycopeptides / Q000302:isolation & purification / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D007118:Immunoassay; D008297:Male; D013058:Mass Spectrometry; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D017430:Prostate-Specific Antigen / Q000737:chemistry / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D013997:Time Factors
chemical_list: D014408:Biomarkers, Tumor; D006020:Glycopeptides; D010446:Peptide Fragments; D020033:Protein Isoforms; D017430:Prostate-Specific Antigen; D019158:N-Acetylneuraminic Acid