Glycopeptide Microarray for Autoantibody Detection in Cancer

Abstract and Introduction

Abstract

Autoantibodies to cancer-associated antigens hold promise as sensitive biomarkers for cancer detection. Based on this hypothesis, and knowing that O-glycans on proteins constitute a source of possible epitopes recognized by autoantibodies, Pedersen and colleagues have generated a glycopeptide array displaying a comprehensive library of glycopeptides and glycoproteins derived from human mucins. The profiling of sera immunoreactivity of colon cancer patients allowed the identification of cancer-associated autoantibodies to various mucin (MUC)1 and MUC4 glycopeptides carrying aberrant glycosylation. This article provides evidence for the value of glycopeptides displaying cancer-associated glycans in diagnostic applications, and opens new avenues for the expansion to other protein glycoforms, as well as to further applications of such a microarray strategy for other post-translational modifications of proteins in the search for cancer biomarker.

Introduction

Glycosylation is the most common posttranslational modification of proteins, and aberrant glycosylation is a hallmark of malignant transformation, being an important source of cancer biomarkers.^[1,2] Cancer-associated glycoconjugates have been used as markers of cancer both at tissue and serum levels (for a review, see^[3]). Mucin-type O-glycosylation is one of the most abundant types of protein post-translational modifications. The biosynthesis of O-glycans on proteins is a complex and regulated process involving more than 50 gene products, mostly glycosyltransferases. Alteration of the levels of expression and Golgi localization of glycosyltransferases, inactivation of molecular chaperones, as well as modification of donor and substrate acceptor substrate availability can lead to formation of truncated O-glycans such as Tn (GalNAcα1-O-Ser/Thr) and STn (NeuAcα2–6GalNAcα1-O-Ser/Thr) antigens.^[1] These antigens are frequently expressed in cancer cells and can generate variants of proteins that lack immunological tolerance, leading to the induction of autoantibodies.^[4] These autoantibodies directed to cancer-associated glycopeptide epitopes constitute attractive targets as cancer biomarkers that can be translated into a practical clinical context, as antibodies have a long half-life in serum, are easy to measure and are stable in blood samples.^[5]

Cite this: Glycopeptide Microarray for Autoantibody Detection in Cancer - Medscape - Aug 01, 2011.

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