Review Glycans as cancer biomarkers ☆ Barbara Adamczyk, Tharmala Tharmalingam, Pauline M. Rudd ⁎ Dublin-Oxford Glycobiology Laboratory, NIBRT—The National Institute for Bioprocessing Research and Training, Fosters Avenue, Mount Merrion, Blackrock, Co. Dublin, Ireland abstract article info Article history: Received 27 September 2011 Received in revised form 11 November 2011 Accepted 1 December 2011 Available online 9 December 2011 Keywords: Glycosylation Biomarker Cancer HPLC Glycan analysis High-throughput Background: Non-invasive biomarkers, such as those from serum, are ideal for disease prognosis, staging and monitoring. In the past decade, our understanding of the importance of glycosylation changes with disease has evolved. Scope of review: We describe potential biomarkers derived from serum glycoproteins for liver, pancreatic, prostate, ovarian, breast, lung and stomach cancers. Methods for glycan analysis have progressed and newly developed high-throughput platform technologies have enabled the analysis of large cohorts of sam- ples in an efficient manner. We also describe this evolution and trends to follow in the future. Major conclusions: Many convincing examples of aberrant glycans associated with cancer have come about from glycosylation analyses. Most studies have been carried out to identify changes in serum glycan profiles or through the isolation and identification of glycoproteins that contain these irregular glycan structures. In a majority of cancers the fucosylation and sialylation expression are found to be significantly modified. There- fore, these aberrations in glycan structures can be utilized as targets to improve existing cancer biomarkers. General significance: The ability to distinguish differences in the glycosylation of proteins between cancer and control patients emphasizes glycobiology as a promising field for potential biomarker identification. Further- more, the high-throughput and reproducible nature of the chromatography platform have highlighted exten- sive applications in biomarker discovery and allowed integration of glycomics with other -omics fields, such as proteomics and genomics, making systems glycobiology a reality. This article is part of a Special Issue en- titled Glycoproteomics. © 2011 Elsevier B.V. All rights reserved. 1. Introduction Cancer is a leading cause of death, with estimations of mortality at 7.6 million worldwide in 2008 [1]. The highest mortality rates occur- ring in patients diagnosed with lung, stomach, liver, colon and breast cancers. Breast cancer is the most diagnosed cancer and leading cause of cancer deaths among women, accounting for 23% of total cancer cases and 14% of cancer deaths. Lung cancer is the leading cause of death in men, comprising 17% of total new cancer cases and 23% of total cancer deaths. With the number of deaths increasing over time, there is an urgent need for clinical markers. Biomarkers can determine the risk of developing a disease, serve as tools for initial di- agnosis and staging diseases, as well as monitor disease progression and the effect of medication. An ideal tumor biomarker would allow a simple blood test to aid clinical decisions. In the past few years, glycomics has been at the forefront of revo- lutionizing biological and medical sciences, holding out the promise of both fully understanding and effectively treating human diseases. Recent research in the glycomics field gave insight into the biological significance of the plasma N-glycome in human health and disease. Special emphasis was placed on exploring the connection between al- tered N-glycosylation of plasma glycoproteins and different diseases, particularly in the study of cancer. It is estimated that over 50% of all human proteins are glycosylated [2]. Glycosylation is found on cell surfaces and in extracellular matri- ces creating the initial point of contact in cellular interactions [3]. Therefore, the effects of disease states on glycan biosynthesis can be more evident than disease related changes to proteins. It is now well established that altered glycosylation varies significantly for can- cer cells compared to normal cells [4–6]. The recognition of glycans as mediators of important biological processes has stimulated growing interests into glycobiology research. The characterization of glycosylation in serum glycoproteins is a challenge due to the heterogeneity of glycoforms. The main methods of glycosylation analysis involve the separation of released glycans by HILIC (hydrophilic-interaction chromatography) HPLC (high perfor- mance liquid chromatography), CE (capillary electrophoresis), lectin affinity and MS (mass spectrometry). Typically HPLC based glycan analysis involves the removal of glycans from glycoproteins by enzy- matic digestion by PNGaseF (peptide N-glycosidase F), labeling with a fluorescent tag (2-aminobenzamine) and subsequent separation Biochimica et Biophysica Acta 1820 (2012) 1347–1353 ☆ This article is part of a Special Issue entitled Glycoproteomics. ⁎ Corresponding author. Tel.: + 353 12158142; fax: + 353 12158116. E-mail address: pauline.rudd@nibrt.ie (P.M. Rudd). 0304-4165/$ – see front matter © 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.bbagen.2011.12.001 Contents lists available at SciVerse ScienceDirect Biochimica et Biophysica Acta journal homepage: www.elsevier.com/locate/bbagen