Cancer-associated autoantibodies to MUC1 and MUC4--a blinded case–control study of colorectal cancer in UK collaborative trial of ovarian cancer screening

TY - JOUR

T1 - Cancer-associated autoantibodies to MUC1 and MUC4--a blinded case–control study of colorectal cancer in UK collaborative trial of ovarian cancer screening

AU - Pedersen, Johannes W

AU - Gentry-Maharaj, Aleksandra

AU - Nøstdal, Alexander

AU - Fourkala, Evangelia-Ourania

AU - Dawnay, Anne

AU - Burnell, Matthew

AU - Zaikin, Alexey

AU - Burchell, Joy

AU - Papadimitriou, Joyce Taylor

AU - Clausen, Henrik

AU - Jacobs, Ian

AU - Menon, Usha

AU - Wandall, Hans H

PY - 2014/5/1

Y1 - 2014/5/1

N2 - 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 before clinical diagnosis, and their utility in cancer screening in the general population. In our 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 randomized to the multimodal arm of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), where women gave annual blood samples for several years. Cases were 97 postmenopausal women who developed colorectal cancer after 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. 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. What's new? Serum antibodies against tumour-associated antigens (TAAs) have shown promise as biomarkers for early cancer detection. In this study, the authors asked whether autoantibodies to specific glycopeptides correlated with colorectal cancer (CRC). They found that an assay for autoantibodies to aberrant glycosylated MUC1 predicted CRC with 95% specificity - but with low sensitivity. However, when the assay combined MUC1 with p53, the sensitivity increased to 32%. These finding suggest that a combination of antibody signatures may eventually enable a biomarker panel for the early detection of CRC.

AB - 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 before clinical diagnosis, and their utility in cancer screening in the general population. In our 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 randomized to the multimodal arm of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), where women gave annual blood samples for several years. Cases were 97 postmenopausal women who developed colorectal cancer after 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. 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. What's new? Serum antibodies against tumour-associated antigens (TAAs) have shown promise as biomarkers for early cancer detection. In this study, the authors asked whether autoantibodies to specific glycopeptides correlated with colorectal cancer (CRC). They found that an assay for autoantibodies to aberrant glycosylated MUC1 predicted CRC with 95% specificity - but with low sensitivity. However, when the assay combined MUC1 with p53, the sensitivity increased to 32%. These finding suggest that a combination of antibody signatures may eventually enable a biomarker panel for the early detection of CRC.

KW - Adult

KW - Autoantibodies

KW - Autoantigens

KW - Case-Control Studies

KW - Colorectal Neoplasms

KW - Early Detection of Cancer

KW - Female

KW - Humans

KW - Male

KW - Middle Aged

KW - Mucin-1

KW - Mucin-4

KW - Ovarian Neoplasms

KW - Protein Array Analysis

KW - Randomized Controlled Trials as Topic

KW - Sensitivity and Specificity

KW - Tumor Markers, Biological

U2 - 10.1002/ijc.28538

DO - 10.1002/ijc.28538

M3 - Journal article

C2 - 24122770

SN - 0020-7136

VL - 134

SP - 2180

EP - 2188

JO - Radiation Oncology Investigations

JF - Radiation Oncology Investigations

IS - 9

ER -