Seromic profiling of colorectal cancer patients with novel glycopeptide microarray
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Standard
Seromic profiling of colorectal cancer patients with novel glycopeptide microarray. / Pedersen, Johannes W; Blixt, Ola; Bennett, Eric P; Tarp, Mads A; Dar, Imran; Mandel, Ulla; Poulsen, Steen S; Pedersen, Anders E; Rasmussen, Susanne; Jess, Per; Clausen, Henrik; Wandall, Hans H.
I: International Journal of Cancer, Bind 128, Nr. 8, 15.04.2011, s. 1860-71.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Seromic profiling of colorectal cancer patients with novel glycopeptide microarray
AU - Pedersen, Johannes W
AU - Blixt, Ola
AU - Bennett, Eric P
AU - Tarp, Mads A
AU - Dar, Imran
AU - Mandel, Ulla
AU - Poulsen, Steen S
AU - Pedersen, Anders E
AU - Rasmussen, Susanne
AU - Jess, Per
AU - Clausen, Henrik
AU - Wandall, Hans H
N1 - Copyright © 2011 UICC.
PY - 2011/4/15
Y1 - 2011/4/15
N2 - Cancer-associated autoantibodies hold promise as sensitive biomarkers for early detection of cancer. Aberrant post-translational variants of proteins are likely to induce autoantibodies, and changes in O-linked glycosylation represent one of the most important cancer-associated post-translational modifications (PTMs). Short aberrant O-glycans on proteins may introduce novel glycopeptide epitopes that can elicit autoantibodies because of lack of tolerance. Technical barriers, however, have hampered detection of such glycopeptide-specific autoantibodies. Here, we have constructed an expanded glycopeptide array displaying a comprehensive library of glycopeptides and glycoproteins derived from a panel of human mucins (MUC1, MUC2, MUC4, MUC5AC, MUC6 and MUC7) known to have altered glycosylation and expression in cancer. Seromic profiling of patients with colorectal cancer identified cancer-associated autoantibodies to a set of aberrant glycopeptides derived from MUC1 and MUC4. The cumulative sensitivity of the array analysis was 79% with a specificity of 92%. The most prevalent of the identified autoantibody targets were validated as authentic cancer immunogens by showing expression of the epitopes in cancer using novel monoclonal antibodies. Our study provides evidence for the value of glycopeptides and other PTM-peptide arrays in diagnostic measures.
AB - Cancer-associated autoantibodies hold promise as sensitive biomarkers for early detection of cancer. Aberrant post-translational variants of proteins are likely to induce autoantibodies, and changes in O-linked glycosylation represent one of the most important cancer-associated post-translational modifications (PTMs). Short aberrant O-glycans on proteins may introduce novel glycopeptide epitopes that can elicit autoantibodies because of lack of tolerance. Technical barriers, however, have hampered detection of such glycopeptide-specific autoantibodies. Here, we have constructed an expanded glycopeptide array displaying a comprehensive library of glycopeptides and glycoproteins derived from a panel of human mucins (MUC1, MUC2, MUC4, MUC5AC, MUC6 and MUC7) known to have altered glycosylation and expression in cancer. Seromic profiling of patients with colorectal cancer identified cancer-associated autoantibodies to a set of aberrant glycopeptides derived from MUC1 and MUC4. The cumulative sensitivity of the array analysis was 79% with a specificity of 92%. The most prevalent of the identified autoantibody targets were validated as authentic cancer immunogens by showing expression of the epitopes in cancer using novel monoclonal antibodies. Our study provides evidence for the value of glycopeptides and other PTM-peptide arrays in diagnostic measures.
U2 - 10.1002/ijc.25778
DO - 10.1002/ijc.25778
M3 - Journal article
C2 - 21344374
VL - 128
SP - 1860
EP - 1871
JO - International Journal of Cancer
JF - International Journal of Cancer
SN - 0020-7136
IS - 8
ER -
ID: 32704884