Increased bisecting N-acetylglucosamine and decreased branched chain glycans of N-linked glycoproteins in expressed prostatic secretions associated with prostate cancer progression

Authors

  • Julius O. Nyalwidhe,

    1. Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA, USA
    2. The Leroy T. Canoles, Jr. Cancer Research Center, Eastern Virginia Medical School Norfolk, VA, USA
    Search for more papers by this author
  • Lucy R. Betesh,

    1. Department of Microbiology and Immunology, Drexel Institute for Biotechnology and Virology, Drexel University College of Medicine, Doylestown, PA, USA
    Search for more papers by this author
  • Thomas W. Powers,

    1. Department of Cell and Molecular Pharmacology and Experimental Therapeutics, MUSC Proteomics Center, Medical University of South Carolina, Charleston, SC, USA
    Search for more papers by this author
  • E. Ellen Jones,

    1. Department of Cell and Molecular Pharmacology and Experimental Therapeutics, MUSC Proteomics Center, Medical University of South Carolina, Charleston, SC, USA
    Search for more papers by this author
  • Krista Y. White,

    1. Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA, USA
    Search for more papers by this author
  • Tanya C. Burch,

    1. Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA, USA
    2. The Leroy T. Canoles, Jr. Cancer Research Center, Eastern Virginia Medical School Norfolk, VA, USA
    Search for more papers by this author
  • Jasmin Brooks,

    1. Department of Cell and Molecular Pharmacology and Experimental Therapeutics, MUSC Proteomics Center, Medical University of South Carolina, Charleston, SC, USA
    Search for more papers by this author
  • Megan T. Watson,

    1. Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA, USA
    2. The Leroy T. Canoles, Jr. Cancer Research Center, Eastern Virginia Medical School Norfolk, VA, USA
    Search for more papers by this author
  • Raymond S. Lance,

    1. The Leroy T. Canoles, Jr. Cancer Research Center, Eastern Virginia Medical School Norfolk, VA, USA
    Search for more papers by this author
  • Dean A. Troyer,

    1. The Leroy T. Canoles, Jr. Cancer Research Center, Eastern Virginia Medical School Norfolk, VA, USA
    Search for more papers by this author
  • O. John Semmes,

    1. Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA, USA
    2. The Leroy T. Canoles, Jr. Cancer Research Center, Eastern Virginia Medical School Norfolk, VA, USA
    Search for more papers by this author
  • Anand Mehta,

    1. Department of Microbiology and Immunology, Drexel Institute for Biotechnology and Virology, Drexel University College of Medicine, Doylestown, PA, USA
    Search for more papers by this author
  • Richard R. Drake

    Corresponding author
    • Department of Cell and Molecular Pharmacology and Experimental Therapeutics, MUSC Proteomics Center, Medical University of South Carolina, Charleston, SC, USA
    Search for more papers by this author

  • Colour Online: See the article online to view Figs. 1, 2 and 4 in colour.

Correspondence: Dr. Richard R. Drake, Department of Cell and Molecular Pharmacology and Experimental Therapeutics, MUSC Proteomics Center, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA

E-mail: draker@musc.edu

Abstract

Purpose

Using prostatic fluids rich in glycoproteins like prostate-specific antigen and prostatic acid phosphatase (PAP), the goal of this study was to identify the structural types and relative abundance of glycans associated with prostate cancer status for subsequent use in emerging MS-based glycopeptide analysis platforms.

Experimental design

A series of pooled samples of expressed prostatic secretions (EPS) and exosomes reflecting different stages of prostate cancer disease were used for N-linked glycan profiling by three complementary methods, MALDI-TOF profiling, normal-phase HPLC separation, and triple quadropole MS analysis of PAP glycopeptides.

Results

Glycan profiling of N-linked glycans from different EPS fluids indicated a global decrease in larger branched tri- and tetra-antennary glycans. Differential exoglycosidase treatments indicated a substantial increase in bisecting N-acetylglucosamines correlated with disease severity. A triple quadrupole MS analysis of the N-linked glycopeptides sites from PAP in aggressive prostate cancer pools was done to cross-reference with the glycan profiling data.

Conclusion and clinical relevance

Changes in glycosylation as detected in EPS fluids reflect the clinical status of prostate cancer. Defining these molecular signatures at the glycopeptide level in individual samples could improve current approaches of diagnosis and prognosis.

Ancillary