Glycan-based biomarkers for diagnosis of cancers and other diseases: Past, present, and future

Glycans are essential biomolecules in regulating human physiology and pathology ranging from signal transduction to microbial infections. Developing complex human diseases, such as cancer, diabetes, and cardiovascular diseases, are a combination of genetic and environmental factors. Genetics dominates embryonic development and the passing of genes to the next generation whereas the information in glycans reflects the impact of internal and external environmental factors, such as diseases, lifestyle, and social factors, on a person's health and disease. The reason behind this is that glycans are not directly encoded in a genetic template. Instead, they are assembled dynamically by hundreds of enzymes organized in more than 10 complex biosynthetic pathways. Any environmental changes affecting enzymatic activities or the availability of high-energy monosaccharide donors in a specific location will disturb the final structure of glycans. The glycan structure-dependent biological activities subsequently enable or disable gene expressions, which partially explain that it is difficult to pinpoint specific genetic defects to aging-associated diseases. Glycan-based biomarkers are currently used for diagnosis of diabetes, cancers, and other complex diseases. We will recapitulate the discovery of glucose, glycated proteins, glycan-, and glycoprotein-based biomarkers followed by summarizing clinically used glycan/glycoprotein-based biomarkers. The potential serum/plasma-derived N- and O-linked glycans as biomarkers will also be discussed.