Cancer biomarkers defined by autoantibody signatures to aberrant O-glycopeptide epitopes Journal Article
| Authors: | Wandall, H. H.; Blixt, O.; Tarp, M. A.; Pedersen, J. W.; Bennett, E. P.; Mandel, U.; Ragupathi, G.; Livingston, P. O.; Hollingsworth, M. A.; Taylor-Papadimitriou, J.; Burchell, J.; Clausen, H. |
| Article 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. ©2010 AACR. |
| Keywords: | controlled study; protein array analysis; major clinical study; case-control studies; cancer diagnosis; antigen expression; ovarian neoplasms; gene overexpression; ovary cancer; breast cancer; models, biological; tumor markers, biological; breast neoplasms; tumor antigen; tumor marker; enzyme linked immunosorbent assay; prostate cancer; prostatic neoplasms; antigen presentation; blood sampling; early diagnosis; microarray analysis; epitope mapping; carcinoma; glycosylation; mucin 1; enzyme-linked immunosorbent assay; autoantibody; antibody detection; clinical trials, phase i as topic; autoantibodies; immunoglobulin g antibody; glycopeptide; glycopeptides; enzyme synthesis; peptide library; hemocyanin; immunization; epitopes; cancer immunology; mucin-1 |
| Journal Title: | Cancer Research |
| Volume: | 70 |
| Issue: | 4 |
| ISSN: | 0008-5472 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2010-02-15 |
| Start Page: | 1306 |
| End Page: | 1313 |
| Language: | English |
| DOI: | 10.1158/0008-5472.can-09-2893 |
| PUBMED: | 20124478 |
| PROVIDER: | scopus |
| PMCID: | PMC5538776 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 15" - "Export Date: 20 April 2011" - "CODEN: CNREA" - "Source: Scopus" |
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