Autoantibodies to MUC1 glycopeptides cannot be used as a screening assay for early detection of breast, ovarian, lung or pancreatic cancer

Burford, Brian; Gentry-Maharaj, A.; Graham, Rosalind; Allen, D S; Pedersen, Jacob; Nudelman, Aaron S.; Blixt, Ola; Fourkala, Evangelia-O; Bueti, Deanna; Dawnay, Anne; Ford, Jane B.; Desai, Roopal; David, Leonor; Trinder, P. K. E.; Acres, Bruce; Schwientek, Tilo; Gammerman, Alexander; Reis, Celso A.; Silva, Liliana; Osório, Hugo; Hallett, Rachel; Wandall, Hans H.; Mandel, Ulla; Hollingsworth, Michael A.; Jacobs, Ian; Fentiman, Ian S.; Clausen, Henrik; Taylor‐Papadimitriou, Joyce; Menon, Usha; Burchell, Joy

doi:10.1038/bjc.2013.214

Cited by 55 publications

(56 citation statements)

References 28 publications

(79 reference statements)

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“…Although many therapeutic antibodies and diagnostic tools are present, however, improvement on the efficacy and specificity of these therapeutic agents in the management of breast cancer is still required [42, 43]. For many years, researches have been focusing on specific glycoforms of MUC1 as diagnostic and therapeutic targets [44, 45].…”

Section: Discussionmentioning

confidence: 99%

Up-regulation of C1GALT1 promotes breast cancer cell growth through MUC1-C signaling pathway

et al. 2015

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Aberrant glycosylation is frequently observed in cancers. Core 1 β1,3-galactosyltransferase (C1GALT1) is an exclusive enzyme in humans that catalyzes the biosynthesis of core 1 O-glycan structure, Gal-GalNAc-O-Ser/Thr, whose expression is commonly up-regulated during tumorigenesis. Little is known about the function of C1GALT1 in breast cancer. This study aims to determine the correlation between C1GALT1 expression and breast cancer clinicopathological features and roles of C1GALT1 in breast cancer malignant phenotypes. Public databases and our data showed that C1GALT1 mRNA and C1GALT1 protein are frequently up-regulated in breast cancer; and increased C1GALT1 expression correlates with higher histological grade and advanced tumor stage. Overexpression of C1GALT1 enhanced breast cancer cell growth, migration, and invasion in vitro as well as tumor growth in vivo. Conversely, C1GALT1 knockdown suppressed these malignant phenotypes. Furthermore, C1GALT1 modulates O-glycan structures on Mucin (MUC) 1 and promotes MUC1-C/β-catenin signaling in breast cancer cells. These findings suggest that C1GALT1 enhances breast cancer malignant progression through promoting MUC1-C/β-catenin signaling pathway. Unveiling the function of C1GALT1 in breast cancer opens new insights to the roles of C1GALT1 and O-glycosylation in tumorigenesis and renders the potential of C1GALT1 as a target of novel therapeutic agent development.

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Section: Discussionmentioning

confidence: 99%

Up-regulation of C1GALT1 promotes breast cancer cell growth through MUC1-C signaling pathway

et al. 2015

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“…They are biochemically well-characterized, and many reagents and techniques are available for their detection, simplifying assay development. Until very recently, several specific autoantibodies have been detected in the sera of patients with advanced-stage breast cancer (14,(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58). However, very few studies have attempted to identify and/or evaluate autoantibodies in node-negative earlystage PBC ( 2 cm) or, more importantly, in preinvasive breast cancer, for which mammography's sensitivity is decreased.…”

Section: Discussionmentioning

confidence: 99%

A Multiparametric Serum Marker Panel as a Complementary Test to Mammography for the Diagnosis of Node-Negative Early-Stage Breast Cancer and DCIS in Young Women

Lacombe

Mangé

Bougnoux

et al. 2014

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: The sensitivity of mammography for the detection of small lesions, including node-negative early-stage (T1N0) primary breast cancer (PBC) and ductal carcinoma in situ (DCIS), is significantly decreased in young patients. From a clinical standpoint, an inconclusive mammogram reflects the inability of clinicians to confidently decide whether patients should be referred for biopsy or for follow-up with repeat imaging.Methods: Specific ELISAs were developed for a panel of 13 well-recognized breast autoantigens (HSP60, FKBP52, PRDX2, PPIA, MUC1, GAL3, PAK2, P53, CCNB1, PHB2, RACK1, RUVBL1, and HER2). Circulating autoantibody levels were measured in a cohort of 396 serum samples from histologically confirmed DCIS (n ¼ 87) or T1N0 PBC (n ¼ 153) and healthy controls (n ¼ 156).Results: Individually, antibodies against CCNB1, FKBP52, GAL3, PAK2, PRDX2, PPIA, P53, and MUC1 demonstrated discriminatory power between breast cancer and healthy control groups. At 90% sensitivity, the overall combined specificity of the autoantibody serum screening test was 42%. Adjustment for higher sensitivities of 95% and 99% resulted in 30% and 21% specificities, respectively (33% and 18% in T1N0 PBC and 28% and 21% in DCIS). Finally, in patients with node-negative early-stage breast cancer younger than 50 years, the autoantibody assay exhibited 59% specificity with a fixed sensitivity at 90%.Conclusions: Our autoantibody panel allows accurate detection of early breast cancer and DCIS, notably in younger patients.Impact: Clinical assessment of this autoantibody panel displays a potential to facilitate clinical management of early-stage breast cancer detection in cases of inconclusive mammogram. Cancer Epidemiol Biomarkers Prev; 23(9); 1834-42. Ó2014 AACR.

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“…Anti-ARS can also be associated with necrotizing myopathy (anti-PL-12 autoantibodies) or pericarditis (anti-PL-7 autoantibodies) [10,11] . Recently studies have indicated that patients with anti-ARS autoantibodies other than those directed to Jo-1 have a different clinical outcome [8,12–14]. Patients with anti-PL-7 and anti-PL-12 autoantibodies frequently have ILD [15], gastrointestinal manifestations and less frequently have myositis compared to anti-Jo-1 positive patients [16] .…”

Section: Clinical Aspects Of the Anti-synthetase Syndromementioning

confidence: 99%

Idiopathic inflammatory myopathies and the anti-synthetase syndrome: A comprehensive review

Mähler

Miller

Fritzler

2014

Autoimmunity Reviews

256

170

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Autoantibodies are a hallmark in the diagnosis of many systemic autoimmune rheumatic diseases (SARD) including idiopathic inflammatory myopathies (IIM). Based on their specificity, autoantibodies in IIM are grouped into myositis specific (MSA) and myositis associated autoantibodies (MAA). Among the MSA, autoantibodies against aminoacyl-tRNA synthetases (ARS) represent the most common antibodies and can be detected in 25–35 % of patients. The presence of ARS and other autoantibodies have become a key feature for classification and diagnosis of IIM and are increasingly used to define clinically distinguishable IIM subsets. For example, anti-ARS autoantibodies are the key features of what has become known as anti-synthetase syndrome (aSS), characterized by multiple organ involvement, primarily interstitial lung disease, often accompanied by myositis, non-erosive arthritis, Raynaud’s phenomenon, fever, and “mechanic’s hands”. Autoantibodies directed to eight different ARS have been described: Jo-1 (histidyl), PL-7 (threonyl), PL-12 (alanyl), OJ (isoleucyl), EJ (glycyl), KS (asparaginyl), Zo (phenylalanyl) and Ha (tyrosyl). Each anti-ARS antibody seems to define a distinctive clinical phenotype. Although several research methods and commercial tests are available, routine testing for anti-ARS autoantibodies (other than anti-Jo-1/histidyl-tRNA synthetase) is not widely available, sometimes leading to delays in diagnosis and poor disease outcomes.

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Autoantibodies to MUC1 glycopeptides cannot be used as a screening assay for early detection of breast, ovarian, lung or pancreatic cancer

Cited by 55 publications

References 28 publications

Up-regulation of C1GALT1 promotes breast cancer cell growth through MUC1-C signaling pathway

Up-regulation of C1GALT1 promotes breast cancer cell growth through MUC1-C signaling pathway

A Multiparametric Serum Marker Panel as a Complementary Test to Mammography for the Diagnosis of Node-Negative Early-Stage Breast Cancer and DCIS in Young Women

Idiopathic inflammatory myopathies and the anti-synthetase syndrome: A comprehensive review

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