Abstract

Colorectal cancer (CRC) is one of the most prevalent cancers worldwide. An increased molecular understanding of the CRC pathology is warranted to gain insights into the underlying molecular and cellular mechanisms of the disease. Altered protein glycosylation patterns are associated with most diseases including malignant transformation. Recent advances in mass spectrometry and bioinformatics have accelerated glycomics research and present a new paradigm for cancer biomarker discovery. Mass spectrometry (MS)-based glycoproteomics and glycomics, therefore, hold considerable promise to improve the discovery of novel biomarkers with utility in disease diagnosis and therapy. This review focuses on the emerging field of glycomics to present a comprehensive review of advances in technologies and their application in studies aimed at discovering novel glycan-based biomarkers. We will also discuss some of the challenges associated with using glycans as biomarkers.

Highlights

  • Colorectal cancer (CRC) is one of the most prevalent cancers, with a major worldwide burden

  • Several studies reported increased expression of β1,6-GlcNAc branched N-glycans in CRC and their association with increased metastasis and invasion, and decreased overall patient survival [50,51,52]. Sialyltransferases represent another important group of glycosyltransferase, which are at least partially responsible for the generation of polylactosamine residues, polysialic acid, terminal and truncated sialylated structures and some ganglioside epitopes, glycosylation features which are all linked to cancer [53]

  • This review provides an overview of the capacity of present-day liquid chromatography (LC)-Mass spectrometry (MS)/MS-based N-glycomics, and the associated challenges, for accurate mapping of the cancer glycome, to gain unique and novel insights into the cancer-associated glycan alterations

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Summary

Introduction

Colorectal cancer (CRC) is one of the most prevalent cancers, with a major worldwide burden. There is growing expectation that new generation of screening tests based on molecular biomarkers originating from biological samples (e.g., patient blood or tissue) would provide a more sensitive, specific and less invasive alternative which would improve patient compliance [5]. It is generally agreed that diagnostic and prognostic markers may reduce patient mortality by yielding an accurate diagnosis and prognosis of early stage disease whereas predictive markers help to assess the patient response to a particular treatment. 5-FU in combination with luecovorin, irinotecan or oxaliplatin [24,25,26], with or without the administration of bevacizumab [27], are some of the standard first-line treatment options available for metastatic CRC patients. Multi-agent combination therapy for treatment of CRC has been shown to improve response rate with greater progression-free survival, but associated with higher cytotoxicity than single agent administration [28]

Overview of N-Glycosylation and Its Biological Roles
Aberrant N-Glycosylation in CRC and Other Cancers
Aim of the Study
LC-Based Separation of N-Glycans
Quantitative Glycomics
Bioinformatics Tools and Glycome-Centric Databases and Resources
Findings
Conclusions
Full Text
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