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

Hans H. Wandall, Ola Blixt, Mads A. Tarp, Johannes W. Pedersen, Eric P. Bennett, Ulla Mandel, Govind Ragupathi, Phil O. Livingston, Michael A Hollingsworth, Joyce Taylor-Papadimitriou, Joy Burchell, Henrik Clausen

Research output: Contribution to journalArticle

173 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1306-1313
Number of pages8
JournalCancer Research
Volume70
Issue number4
DOIs
StatePublished - Feb 15 2010

Fingerprint

Glycopeptides
Tumor Biomarkers
Autoantibodies
Epitopes
Neoplasms
Early Detection of Cancer
Immunoglobulin G
Biomarkers
Antibodies
Mucins
Serum
Ovarian Neoplasms
Prostatic Neoplasms
Enzyme-Linked Immunosorbent Assay
Breast Neoplasms
Antigens
Peptides
Proteins

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Wandall, H. H., Blixt, O., Tarp, M. A., Pedersen, J. W., Bennett, E. P., Mandel, U., ... Clausen, H. (2010). Cancer biomarkers defined by autoantibody signatures to aberrant O-glycopeptide epitopes. Cancer Research, 70(4), 1306-1313. https://doi.org/10.1158/0008-5472.CAN-09-2893

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, 15.02.2010, p. 1306-1313.

Research output: Contribution to journalArticle

Wandall, HH, Blixt, O, Tarp, MA, Pedersen, JW, Bennett, EP, Mandel, U, Ragupathi, G, Livingston, PO, Hollingsworth, MA, Taylor-Papadimitriou, J, Burchell, J & Clausen, H 2010, 'Cancer biomarkers defined by autoantibody signatures to aberrant O-glycopeptide epitopes', Cancer Research, vol. 70, no. 4, pp. 1306-1313. https://doi.org/10.1158/0008-5472.CAN-09-2893
Wandall HH, Blixt O, Tarp MA, Pedersen JW, Bennett EP, Mandel U et al. Cancer biomarkers defined by autoantibody signatures to aberrant O-glycopeptide epitopes. Cancer Research. 2010 Feb 15;70(4):1306-1313. https://doi.org/10.1158/0008-5472.CAN-09-2893
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. / Cancer biomarkers defined by autoantibody signatures to aberrant O-glycopeptide epitopes. In: Cancer Research. 2010 ; Vol. 70, No. 4. pp. 1306-1313.
@article{1403a2fbd04b425a8f24fadff9413df6,
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.",
author = "Wandall, {Hans H.} and Ola Blixt and Tarp, {Mads A.} and Pedersen, {Johannes W.} and Bennett, {Eric P.} and Ulla Mandel and Govind Ragupathi and Livingston, {Phil O.} and Hollingsworth, {Michael A} and Joyce Taylor-Papadimitriou and Joy Burchell and Henrik Clausen",
year = "2010",
month = "2",
day = "15",
doi = "10.1158/0008-5472.CAN-09-2893",
language = "English (US)",
volume = "70",
pages = "1306--1313",
journal = "Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "4",

}

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.

UR - http://www.scopus.com/inward/record.url?scp=76749087478&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=76749087478&partnerID=8YFLogxK

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

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

M3 - Article

C2 - 20124478

AN - SCOPUS:76749087478

VL - 70

SP - 1306

EP - 1313

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 4

ER -