title: Cancer biomarkers defined by autoantibody signatures to aberrant O-glycopeptide epitopes.
abstract: 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.
authors.affiliation: Center for Glycomics, Departments of Cellular and Molecular Medicine and Oral Diagnostics, University of Copenhagen, Blegdamsvej 3, Copenhagen 2200 N, Denmark. hhw@sund.ku.dk
authors.forename: Hans H
authors.initials: HH
authors.lastname: Wandall
authors.forename: Ola
authors.initials: O
authors.lastname: Blixt
authors.forename: Mads A
authors.initials: MA
authors.lastname: Tarp
authors.forename: Johannes W
authors.initials: JW
authors.lastname: Pedersen
authors.forename: Eric P
authors.initials: EP
authors.lastname: Bennett
authors.forename: Ulla
authors.initials: U
authors.lastname: Mandel
authors.forename: Govind
authors.initials: G
authors.lastname: Ragupathi
authors.forename: Phil O
authors.initials: PO
authors.lastname: Livingston
authors.forename: Michael A
authors.initials: MA
authors.lastname: Hollingsworth
authors.forename: Joyce
authors.initials: J
authors.lastname: Taylor-Papadimitriou
authors.forename: Joy
authors.initials: J
authors.lastname: Burchell
authors.forename: Henrik
authors.initials: H
authors.lastname: Clausen
mesh_terms: D017951:Antigen Presentation / Q000502:physiology; D001323:Autoantibodies / Q000032:analysis* / Q000097:blood; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000276:immunology*; D001943:Breast Neoplasms / Q000097:blood / Q000276:immunology; D002277:Carcinoma / Q000097:blood / Q000276:immunology; D016022:Case-Control Studies; D017321:Clinical Trials, Phase I as Topic; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D018604:Epitope Mapping / Q000379:methods; D000939:Epitopes / Q000032:analysis*; D005260:Female; D006020:Glycopeptides / Q000276:immunology*; D006801:Humans; D007114:Immunization; D008297:Male; D008954:Models, Biological; D018396:Mucin-1 / Q000737:chemistry / Q000276:immunology; D010051:Ovarian Neoplasms / Q000097:blood / Q000276:immunology; D019151:Peptide Library; D011471:Prostatic Neoplasms / Q000097:blood / Q000276:immunology; D040081:Protein Array Analysis / Q000295:instrumentation / Q000379:methods
chemical_list: D001323:Autoantibodies; D014408:Biomarkers, Tumor; D000939:Epitopes; D006020:Glycopeptides; C060192:MUC1 protein, human; D018396:Mucin-1; D019151:Peptide Library