Early detection of cancer in the general population: a blinded case–control study of p53 autoantibodies in colorectal cancer

Abstract

Background:Recent reports from cancer screening trials in high-risk populations suggest that autoantibodies can be detected before clinical diagnosis. However, there is minimal data on the role of autoantibody signatures in cancer screening in the general population.Methods:Informative p53 peptides were identified in sera from patients with colorectal cancer using an autoantibody microarray with 15-mer overlapping peptides covering the complete p53 sequence. The selected peptides were evaluated in a blinded case–control study using stored serum from the multimodal arm of the United Kingdom Collaborative Trial of Ovarian Cancer Screening where women gave annual blood samples. Cases were postmenopausal women who developed colorectal cancer following recruitment, with 2 or more serum samples preceding diagnosis. Controls were age-matched women with no history of cancer.Results:The 50 640 women randomised to the multimodal group were followed up for a median of 6.8 (inter-quartile range 5.9–8.4) years. Colorectal cancer notification was received in 101 women with serial samples of whom 97 (297 samples) had given consent for secondary studies. They were matched 1 : 1 with 97 controls (296 serial samples). The four most informative peptides identified 25.8% of colorectal cancer patients with a specificity of 95%. The median lead time was 1.4 (range 0.12–3.8) years before clinical diagnosis.Conclusion:Our findings suggest that in the general population, autoantibody signatures are detectable during preclinical disease and may be of value in cancer screening. In colorectal cancer screening in particular, where the current need is to improve compliance, it suggests that p53 autoantibodies may contribute towards risk stratification.

Colorectal Cancer Circulating Biomarkers

“…The authors found that the presence of autoantibodies to both proteins was associated to a better outcome of the disease. Finally, in another recent study, an association of high levels of autoantibodies to the aberrant glycopeptide MUC4TR5 with a risk of death in CRC patients has been observed (Pedersen et al 2013).…”

“…A predictor panel composed of a panel of 7 CRC-specific TAAs achieved an AUC of 90 % and a sensitivity of 88.2 % and specificity of 82.6 % for early stages (Duke's stage A and B) (Barderas et al 2012). It has also been reported that humoral responses to p53 can appear in normal-risk individuals between 1.0 and 3.8 years before clinical diagnosis of CRC (Pedersen et al 2013).…”

Cancer serum biomarkers based on aberrant post-translational modifications of glycoproteins: Clinical value and discovery strategies

“…This approach has been used to develop assays which can detect different types of cancer, such as breast cancer [13][14][15], lung cancer [16][17][18] and colorectal cancer [19]. In these assays, autoantibodies to p53, c-myc, HER-2, NY-ESO-1, BRCA1, BRCA2, MUC1, cyclin B1, CEA, CAGE, GBU4-5, annexin 1, SOX2, HuD, MAGE A4 and FOXP3, were studied and specific autoantibodies have been reported to be present in sera of patients before clinical diagnosis of cancer.…”

Integrated proteo-genomic approach for early diagnosis and prognosis of cancer

“…These antigens are frequently expressed in cancer cells and can generate variants proteins that lack immunological tolerance, leading to the induction of autoantibodies. By employing glycopeptide array displaying a comprehensive library of glycopeptides and glycoproteins derived from human mucins MUC1 and MUC4 could be used as biomarkers for early detection of many types of cancer with high specificity [76,77].…”