Cancer Biomarkers Defined by Autoantibody Signatures to Aberrant O-Glycopeptide Epitopes

DOI PDF 7 Citations
  • Hans H. Wandall
    Authors' Affiliations: 1Center for Glycomics, Departments of Cellular and Molecular Medicine and Oral Diagnostics, University of Copenhagen, Copenhagen, Denmark; 2Department of Medicine, Melanoma and Sarcoma Service, Memorial Sloan-Kettering Cancer Center, New York, New York; 3Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska, Omaha, Nebraska; and 4King's College School of Medicine, Guy's Hospital London, London, United Kingdom
  • Ola Blixt
    Authors' Affiliations: 1Center for Glycomics, Departments of Cellular and Molecular Medicine and Oral Diagnostics, University of Copenhagen, Copenhagen, Denmark; 2Department of Medicine, Melanoma and Sarcoma Service, Memorial Sloan-Kettering Cancer Center, New York, New York; 3Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska, Omaha, Nebraska; and 4King's College School of Medicine, Guy's Hospital London, London, United Kingdom
  • Mads A. Tarp
    Authors' Affiliations: 1Center for Glycomics, Departments of Cellular and Molecular Medicine and Oral Diagnostics, University of Copenhagen, Copenhagen, Denmark; 2Department of Medicine, Melanoma and Sarcoma Service, Memorial Sloan-Kettering Cancer Center, New York, New York; 3Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska, Omaha, Nebraska; and 4King's College School of Medicine, Guy's Hospital London, London, United Kingdom
  • Johannes W. Pedersen
    Authors' Affiliations: 1Center for Glycomics, Departments of Cellular and Molecular Medicine and Oral Diagnostics, University of Copenhagen, Copenhagen, Denmark; 2Department of Medicine, Melanoma and Sarcoma Service, Memorial Sloan-Kettering Cancer Center, New York, New York; 3Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska, Omaha, Nebraska; and 4King's College School of Medicine, Guy's Hospital London, London, United Kingdom
  • Eric P. Bennett
    Authors' Affiliations: 1Center for Glycomics, Departments of Cellular and Molecular Medicine and Oral Diagnostics, University of Copenhagen, Copenhagen, Denmark; 2Department of Medicine, Melanoma and Sarcoma Service, Memorial Sloan-Kettering Cancer Center, New York, New York; 3Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska, Omaha, Nebraska; and 4King's College School of Medicine, Guy's Hospital London, London, United Kingdom
  • Ulla Mandel
    Authors' Affiliations: 1Center for Glycomics, Departments of Cellular and Molecular Medicine and Oral Diagnostics, University of Copenhagen, Copenhagen, Denmark; 2Department of Medicine, Melanoma and Sarcoma Service, Memorial Sloan-Kettering Cancer Center, New York, New York; 3Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska, Omaha, Nebraska; and 4King's College School of Medicine, Guy's Hospital London, London, United Kingdom
  • Govind Ragupathi
    Authors' Affiliations: 1Center for Glycomics, Departments of Cellular and Molecular Medicine and Oral Diagnostics, University of Copenhagen, Copenhagen, Denmark; 2Department of Medicine, Melanoma and Sarcoma Service, Memorial Sloan-Kettering Cancer Center, New York, New York; 3Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska, Omaha, Nebraska; and 4King's College School of Medicine, Guy's Hospital London, London, United Kingdom
  • Phil O. Livingston
    Authors' Affiliations: 1Center for Glycomics, Departments of Cellular and Molecular Medicine and Oral Diagnostics, University of Copenhagen, Copenhagen, Denmark; 2Department of Medicine, Melanoma and Sarcoma Service, Memorial Sloan-Kettering Cancer Center, New York, New York; 3Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska, Omaha, Nebraska; and 4King's College School of Medicine, Guy's Hospital London, London, United Kingdom
  • Michael A. Hollingsworth
    Authors' Affiliations: 1Center for Glycomics, Departments of Cellular and Molecular Medicine and Oral Diagnostics, University of Copenhagen, Copenhagen, Denmark; 2Department of Medicine, Melanoma and Sarcoma Service, Memorial Sloan-Kettering Cancer Center, New York, New York; 3Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska, Omaha, Nebraska; and 4King's College School of Medicine, Guy's Hospital London, London, United Kingdom
  • Joyce Taylor-Papadimitriou
    Authors' Affiliations: 1Center for Glycomics, Departments of Cellular and Molecular Medicine and Oral Diagnostics, University of Copenhagen, Copenhagen, Denmark; 2Department of Medicine, Melanoma and Sarcoma Service, Memorial Sloan-Kettering Cancer Center, New York, New York; 3Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska, Omaha, Nebraska; and 4King's College School of Medicine, Guy's Hospital London, London, United Kingdom
  • Joy Burchell
    Authors' Affiliations: 1Center for Glycomics, Departments of Cellular and Molecular Medicine and Oral Diagnostics, University of Copenhagen, Copenhagen, Denmark; 2Department of Medicine, Melanoma and Sarcoma Service, Memorial Sloan-Kettering Cancer Center, New York, New York; 3Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska, Omaha, Nebraska; and 4King's College School of Medicine, Guy's Hospital London, London, United Kingdom
  • Henrik Clausen
    Authors' Affiliations: 1Center for Glycomics, Departments of Cellular and Molecular Medicine and Oral Diagnostics, University of Copenhagen, Copenhagen, Denmark; 2Department of Medicine, Melanoma and Sarcoma Service, Memorial Sloan-Kettering Cancer Center, New York, New York; 3Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska, Omaha, Nebraska; and 4King's College School of Medicine, Guy's Hospital London, London, United Kingdom

Description

<jats:title>Abstract</jats:title> <jats:p>Autoantibodies to cancer antigens hold promise as biomarkers for early detection of cancer. Proteins that are aberrantly processed in cancer cells are likely to present autoantibody targets. The extracellular mucin MUC1 is overexpressed and aberrantly glycosylated in many cancers; thus, we evaluated whether autoantibodies generated to aberrant O-glycoforms of MUC1 might serve as sensitive diagnostic biomarkers for cancer. Using an antibody-based glycoprofiling ELISA assay, we documented that aberrant truncated glycoforms were not detected in sera of cancer patients. An O-glycopeptide microarray was developed that detected IgG antibodies to aberrant O-glycopeptide epitopes in patients vaccinated with a keyhole limpet hemocyanin–conjugated truncated MUC1 peptide. We detected cancer-associated IgG autoantibodies in sera from breast, ovarian, and prostate cancer patients against different aberrent O-glycopeptide epitopes derived from MUC1. These autoantibodies represent a previously unaddressed source of sensitive biomarkers for early detection of cancer. The methods we have developed for chemoenzymatic synthesis of O-glycopeptides on microarrays may allow for broader mining of the entire cancer O-glycopeptidome. Cancer Res; 70(4); 1306–13</jats:p>

Journal

  • Cancer Research

    Cancer Research 70 (4), 1306-1313, 2010-02-14

    American Association for Cancer Research (AACR)

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