Cancer biomarkers defined by autoantibody signatures to aberrant O-glycopeptide epitopes
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Cancer biomarkers defined by autoantibody signatures to aberrant O-glycopeptide epitopes. / Wandall, Hans H; Blixt, Ola; Tarp, Mads A; Pedersen, Johannes W; Bennett, Eric P; Mandel, Ulla; Ragupathi, Govind; Livingston, Phil O; Hollingsworth, Michael A; Taylor-Papadimitriou, Joyce; Burchell, Joy; Clausen, Henrik.
In: Cancer Research, Vol. 70, No. 4, 2010, p. 1306-13.Research output: Contribution to journal › Journal article › Research › peer-review
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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
Y1 - 2010
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
VL - 70
SP - 1306
EP - 1313
JO - Cancer Research
JF - Cancer Research
SN - 0008-5472
IS - 4
ER -
ID: 18553710