Cancer biomarkers defined by autoantibody signatures to aberrant O-glycopeptide epitopes

TY - JOUR

T1 - Cancer biomarkers defined by autoantibody signatures to aberrant O-glycopeptide epitopes

AU - Wandall, Hans H

AU - Blixt, Ola

AU - Tarp, Mads A

AU - Pedersen, Johannes W

AU - Bennett, Eric P

AU - Mandel, Ulla

AU - Ragupathi, Govind

AU - Livingston, Phil O

AU - Hollingsworth, Michael A

AU - Taylor-Papadimitriou, Joyce

AU - Burchell, Joy

AU - Clausen, Henrik

PY - 2010/2/15

Y1 - 2010/2/15

N2 - 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.

AB - 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.

U2 - 10.1158/0008-5472.CAN-09-2893

DO - 10.1158/0008-5472.CAN-09-2893

M3 - Journal article

C2 - 20124478

SN - 0008-5472

VL - 70

SP - 1306

EP - 1313

JO - Cancer Research

JF - Cancer Research

IS - 4

ER -