Aberrant glycosylation associated with enzymes as cancer biomarkers

Abstract

BackgroundOne of the new roles for enzymes in personalized medicine builds on a rational approach to cancer biomarker discovery using enzyme-associated aberrant glycosylation. A hallmark of cancer, aberrant glycosylation is associated with differential expressions of enzymes such as glycosyltransferase and glycosidases. The aberrant expressions of the enzymes in turn cause cancer cells to produce glycoproteins with specific cancer-associated aberrations in glycan structures.ContentIn this review we provide examples of cancer biomarker discovery using aberrant glycosylation in three areas. First, changes in glycosylation machinery such as glycosyltransferases/glycosidases could be used as cancer biomarkers. Second, most of the clinically useful cancer biomarkers are glycoproteins. Discovery of specific cancer-associated aberrations in glycan structures of these existing biomarkers could improve their cancer specificity, such as the discovery of AFP-L3, fucosylated glycoforms of AFP. Third, cancer-associated aberrations in glycan structures provide a compelling rationale for discovering new biomarkers using glycomic and glycoproteomic technologies.SummaryAs a hallmark of cancer, aberrant glycosylation allows for the rational design of biomarker discovery efforts. But more important, we need to translate these biomarkers from discovery to clinical diagnostics using good strategies, such as the lessons learned from translating the biomarkers discovered using proteomic technologies to OVA 1, the first FDA-cleared In Vitro Diagnostic Multivariate Index Assay (IVDMIA). These lessons, providing important guidance in current efforts in biomarker discovery and translation, are applicable to the discovery of aberrant glycosylation associated with enzymes as cancer biomarkers as well.

Human Natural Killer-1 Sulfotransferase (HNK-1ST)-induced Sulfate Transfer Regulates Laminin-binding Glycans on α-Dystroglycan

“…The external region of a cell membrane, known as the glycocalyx, is dominated by glycosylated molecules, which have important roles in these interactions (2). Therefore, the aberrant expression of various genes involved in glycan synthesis or degradation, which causes compositional changes of the glycocalyx, is frequently associated with malignant transformation (3)(4)(5). Recently, Zhao et al (6) reported the expression of human natural killer-1 sulfotransferase (HNK-1ST) to be strongly up-regulated in several subsets of murine and human melanoma cells during retinoic acid (RA) 2 mediated differentiation.…”

Lectin from Agrocybe aegerita as a Glycophenotype Probe for Evaluation of Progression and Survival in Colorectal Cancer

“…However, the clinical useful markers based on genomics and proteomics remain limited. In recent years, aberrant glycosylation has been recognized as a cellular hallmark event during carcinogenesis (Reis et al, 2010;Adamczyk et al, 2011), and it has been a topic for well characterization of tumor and better understanding the mechanism (Meany et al, 2011). Both N-and O-linked glycoproteins have been shown to be altered in a wide range of cancers, including CRC.…”

The advancements of genomics and data integration in sarcoma research

“…A wealth of proteomic and metabolomic technologies has been developed to gain insight into some of these downstream mechanisms. Post-translational regu latory mechanisms of interest, including proteinprotein interactions, glycosylation, phosphorylation, and ubiquitination, are being studied extensively to shed light on aberrations associated with diseased states [121][122][123][124] .…”