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Cancer associated auto-antibodies to MUC1 and MUC4 - A blinded case control study of colorectal cancer in UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS)

Pedersen, JW; Gentry-Maharaj, A; Nøstdal, A; Fourkala, EO; Dawnay, A; Burnell, M; Zaikin, A; ... Wandall, HH; + view all (2013) Cancer associated auto-antibodies to MUC1 and MUC4 - A blinded case control study of colorectal cancer in UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). International Journal of Cancer , 134 (9) pp. 2180-2188. 10.1002/ijc.28538. Green open access

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Abstract

Recent reports suggest that autoantibodies directed to aberrantly glycosylated mucins, in particular MUC1 and MUC4, are found in patients with colorectal cancer. There is, however, limited information on the autoantibody levels prior to clinical diagnosis, and their utility in cancer screening in the general population. In this study, we have generated O-glycosylated synthetic MUC1 and MUC4 peptides in vitro, to mimic cancer associated glycoforms, and displayed these on microarrays. The assay's performance was tested through an initial screening of serum samples taken from patients at the time of colorectal cancer diagnosis and healthy controls. Subsequently the selected biomarkers were evaluated in a blinded nested case control study, using stored serum samples from among the 50,640 women randomised to the multimodal arm of the UKCTOCS, where women gave annual blood samples for several years. Cases were 97 postmenopausal women who developed colorectal cancer following recruitment, and were age-matched to 97 women without any history of cancer. MUC1-STn and MUC1-Core3 IgG autoantibodies identified cases with 8.2% and 13.4% sensitivity, respectively, at 95% specificity. IgA to MUC4-glycoforms were unable to discriminate between cases and controls in the UKCTOCS sera. Additional analysis was undertaken by combining the data of MUC1-STn and MUC1-Core3 with previously generated data on autoantibodies to p53 peptides, which increased the sensitivity to 32.0% at 95% specificity in the UKCTOCS set. These findings suggest that a combination of antibody signatures may have a role as part of a biomarker panel for the early detection of colorectal cancer.

Type: Article
Title: Cancer associated auto-antibodies to MUC1 and MUC4 - A blinded case control study of colorectal cancer in UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS)
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/ijc.28538
Publisher version: http://dx.doi.org/10.1002/ijc.28538
Language: English
Additional information: This is an open access article under the terms of the Creative Commons Attribution NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
Keywords: MUC1, MUC4, autoantibodies, biomarkers, cancer, colon, early diagnosis, glycosylation, microarray, rectum, seromic profiling
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health > Womens Cancer
URI: https://discovery.ucl.ac.uk/id/eprint/1410657
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