Aberrant glycosylation associated with enzymes as cancer biomarkers

In 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.As 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.Enzymes were one of the first protein molecules used as cancer biomarkers. Discovered in the early 1980s as a cancer biomarker for the early detection of prostate cancer, prostate specific antigen (PSA) is a serine protease[1]. With the exception of PSA, the increase in enzymatic activities or protein mass is not sensitive or specific enough for early detection of cancer[1]. Nevertheless, enzymes as cancer biomarkers have profound clinical utilities in the personalized approach to cancer diagnosis and treatment: Her-2/neu, a cell membrane surface-bound receptor tyrosine kinase, is a predictive marker to select breast cancer patients for treatment with trastuzumab (Herceptin)[2,3].