Ovarian cancer is the most lethal of all gynaecological cancers among women. Serum CA125 is the only biomarker that is used routinely and there is a need for further complementary biomarkers both in terms of sensitivity and specificity.N-glycosylation changes in ovarian cancer serum glycoproteins include a decrease in galactosylation of IgG and an increase in sialyl Lewis X (SLex) on haptoglobin &#x3b2;-chain, &#x3b1;1-acid glycoprotein and &#x3b1;1-antichymotrypsin. These changes are also present in chronic inflammation but not in malignant melanoma, where there are low levels of inflammatory processes. Acute phase proteins carrying increased amounts of SLex have an increased half-life. Sialylation of acute phase proteins also decreases apoptosis favouring survival of cancer cells. Cancer cells produce inflammatory cytokines which influence glycosylation processing in liver parenchymal cells. Altered glycosylation of the acute phase protein transferrin plays an important role in iron homeostasis. Glycosylated transferrin and its glycans have anti-apoptotic properties and many transferrin receptors in carcinoma could play a role in development of anaemia. Decreased galactosylation and sialylation of IgG increases the cytotoxicity of natural killer cells and complement activation via mannose-binding lectin (MBL). Altered glycosylation of acute phase proteins and IgG suggests that cancer regulates certain pathways favouring cancer cells survival.

Radka Saldova

Mark R. Wormald

Raymond A. Dwek

Pauline M. Rudd

Glycosylation Changes on Serum Glycoproteins in Ovarian Cancer May Contribute to Disease Pathogenesis

Once dismissed as just the icing on the cake, sugar molecules are emerging as vital components in life&#x2019;s intricate machinery. Our understanding of their function within the context of the proteins and lipids to which they are attached has matured rapidly, and with it the far reaching clinical implications are becoming understood.Recent advances in high-throughput glycomic techniques, glyco biomarker profiling, glyco-bioinformatics and development of increasingly sophisticated glyco-arrays, combined with our increased understanding of the molecular details of glycosylation have facilitated the linkage between aberrant glycosylation and human diseases, and highlighted the possibility of using glyco-biomarkers as potential determinants of disease and its progression.The focus of this review is to give an insight into the biological significance of these glycomodifications, highlight some specific examples of glyco-biomarkers in relation to autoimmunity and in particular rheumatoid arthritis, and to explore the exciting possibility of exploiting these for diagnostic and prognostic strategies.

Azita Alavi

John S. Axford

Glyco-biomarkers: Potential Determinants of Cellular Physiology and Pathology

Spontaneously mutated multiple oncogenes and/or tumor suppressor genes in colon epithelial cell and its progeny, may cause proliferation out of control and create benign colon neoplasm (colon polyp). If additional mutations involve genes responsible for cell adhesion and movement, aberrant epithelial cells may become malignant (colon cancer) and invade surrounding and remote tissues, creating secondary tumors called metastases.Incidence of colorectal cancer dramatically increases at 50&#x2013;65 year of age. In Europe in 2006 colorectal cancer consisted 12.9&#x25; of all cancers and caused 207 400 deaths.To laboratory detection and monitoring of colon cancer are used tumor markers. Tumor markers are substances produced by the body in response to cancer, or by cancer tissue itself. Glycoconjugate markers for colon cancer include aberrant: mucins covering the surface of the colon epithelial cells, cadherins, selectins and Ig &#x2013;like adhesion molecules mediating cell-cell adhesion, integrins and integral membrane proteoglycans responsible for adhesion of colon epithelial cells to extracellular matrix, glycoconjugate components of ECM, as well as lysosomal membrane glycoproteins and exoglycosidases.Detection of colon cancer at early non malignant stage is crucial in its prevention and eradication. As colon cancer is the effect of accumulation many somatic mutations in oncogens, supressors, mismatch repair genes and many genes responsible for posttranslational modifications of proteins, multidirectional approach should be applied for its detection. A glycobiological approach to diagnosis and treatment of colorectal cancer should be directed to detection changes in glycosylation accompanying every step of colon cancer progression, and correlation between changes in glycosylation and tumor progression.

S&#x142;awomir Dariusz Szajda

Anna Jankowska

Krzysztof Zwierz

Carbohydrate Markers in Colon Carcinoma

Marion Boland

Editorial

Prostate cancer is a leading cause of cancer death among men. Currently available screening test measures prostate-specific antigen (PSA) to detect prostate cancer. However, this test produces false positive values that often lead to negative biopsies. Therefore, a more reliable diagnostic tool is needed. Glycans in serum are of particular interest as around half of all proteins are glycosylated. In this study, N-linked glycans were enzymatically released by PNGase F from prostate epithelial cell lines (pRNS) expressing wild type or mutant androgen receptors and a small set of human serum samples. Released glycans were purified and partitioned into neutral and acidic components by solid phase extraction (SPE) using graphitized carbon cartridges. The SPE fractions were analyzed by matrix-assisted laser desorption/ionization Fourier transform ion cyclotron resonance mass spectrometry (MALDI FT-ICR MS). Significant changes in some high-mannose and fucosylated biantennary complex N-linked glycans were observed in the serum of prostate cancer patients.

Maria Lorna A. de Leoz

Hyun Joo An

Scott Kronewitter

Jaehan Kim

Sean Beecroft

Ruth Vinall

Suzanne Miyamoto

Ralph de Vere White

Kit S. Lam

Carlito Lebrilla

Glycomic Approach for Potential Biomarkers on Prostate Cancer: Profiling of N-Linked Glycans in Human Sera and pRNS Cell Lines

Changes in N-linked glycosylation are known to occur during the development of various diseases. For example, increased branching of oligosaccharides has been associated with cancer metastasis and has been correlated to tumor progression in human cancers of the breast, colon and melanomas. Increases in core fucosylation have also been associated with the development of hepatocellular carcinoma (HCC). Recently, changes in both the total serum glycome and the glycosylation of specific IgG molecules have been observed in people with liver fibrosis and cirrhosis. The mechanisms by which changes in glycosylation are observed and their use as biomarkers of disease will be discussed.

Anand Mehta

Timothy M. Block

Fucosylated Glycoproteins as Markers of Liver Disease

The lack of specific and sensitive tumour markers for early detection of cancer is driving a search for new approaches that could identify biomarkers. Markers are needed to alert clinicians at the early stages of tumourogenesis, before the cancer has metastasized, when the therapeutic drugs are more effective. Most tumour markers currently used in clinics are serum glycoproteins, frequently highly glycosylated mucins. Typically, the disease marker is the protein and not the glycan moiety of the corresponding glycoprotein or mucin. The increasing knowledge of the role of glycans in cancer suggests that further studies may assist both in determining their role in every step of tumour progression, and in the design of new therapeutic and diagnosic approaches. Detection of the altered glycans in serum tumour glycoproteins could be a way to achieve specificity in tumour detection. In this review, we focus on the glycan changes of two serum glycoproteins, prostate specific antigen - currently used as a tumour marker of prostate cancer - and human pancreatic ribonuclease in pancreatic adenocarcinoma. The detection of glycan changes, associated with subsets of glycoforms in serum glycoproteins that are specific to the tumour situation, could be the basis for developing more specific biomarkers.

Rosa Peracaula

S&#xed;lvia Barrab&#xe9;s

Ariadna Sarrats

Rafael de Llorens

Altered Glycosylation in Tumours Focused to Cancer Diagnosis

Inflammatory diseases are accompanied by numerous changes at the site of inflammation as well as many systemic physiological and biochemical changes. In the past two decades more and more attention is being paid to changes in glycosylation and in this review we describe some of the changes found on main serum proteins (&#x3b1;1-acid glycoprotein, immunoglobulin G, immunoglobulin A, transferrin, haptoglobin, &#x3b1;2-macroglobulin, C-reactive protein, and others). Molecular background and physiological importance of most of these changes are yet to be discovered, but it is evident that glycosylation plays an important role in the inflammatory response. Maybe the greatest value of these changes currently lays in their potential diagnostic and prognostic usage, either in combination with current diagnostic markers or on their own. However, determining glycan structures is still technically too complex for most clinical laboratories and further efforts have to be made to develop simple analytical tools to study changes in glycosylation.

Olga Gornik

Gordan Lauc

Glycosylation of Serum Proteins in Inflammatory Diseases

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Disease Markers publishes papers related to the identification of disease markers, the elucidation of their role and mechanism, as well as their application in the prognosis, diagnosis and treatment of diseases.

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Chief Editor Paola Gazzaniga is an Associate Professor in the Department of Molecular Medicine at Sapienza University of Rome, Italy. Her core research focuses on liquid biopsies in patients with solid tumors.

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Disease Markers

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	Pauline M. Rudd