Abstract
Cancer is a major cause of death in both developing and developed countries. Early detection and efficient therapy can greatly enhance survival. Aberrant glycosylation has been recognized to be one of the hallmarks of cancer as glycans participate in many cancer-associated events. Cancer-associated glycosylation changes often involve sialic acids which play important roles in cell-cell interaction, recognition and immunological response. This review aims at giving a comprehensive overview of the literature on changes of sialylation in serum of cancer patients. Furthermore, the methods available to measure serum and plasma sialic acids as well as possible underlying biochemical mechanisms involved in the serum sialylation changes are surveyed. In general, total serum sialylation levels appear to be increased with various malignancies and show a potential for clinical applications, especially for disease monitoring and prognosis. In addition to overall sialic acid levels and the amount of sialic acid per total protein, glycoprofiling of specific cancer-associated glycoproteins, acute phase proteins and immunoglobulins in serum as well as the measurements of sialylation-related enzymes such as sialidases and sialyltransferases have been reported for early detection of cancer, assessing cancer progression and improving prognosis of cancer patients. Moreover, sialic-acid containing glycan antigens such as CA19–9, sialyl Lewis X and sialyl Tn on serum proteins have also displayed their value in cancer diagnosis and management whereby increased levels of these factors positively correlated with metastasis or poor prognosis.
Highlights
Cancer, an increasing burden worldwide, is a major cause of death in both developing and developed countries
This study found that elevation of all three serum markers was positively related to tumor presence and negatively associated with response to anticancer treatment, making high levels of these markers at diagnosis an indicator of poor prognosis [157]
Serum/plasma sialylation changes in cancer patients have been studied to evaluate their potential as tumor marker
Summary
An increasing burden worldwide, is a major cause of death in both developing and developed countries. As a result, monitoring serum/plasma factors such as overall sialic acid content, sialidase activity and sialyltransferase expression, as well as sialylation changes on specific serum glycoproteins may have useful clinical applications for the detection, staging and prognosis of different diseases and cancers as reviewed in the following. In prostate cancer, determining the concentration of prostate specific antigen (PSA) alone has displayed limitations in early detection [87].PSAspecific glycosylation changes in serum from prostate cancer patients compared with controls have been characterized by employing matrix-assisted laser desorption/ionization-timeof-flight-mass spectrometry (MALDI-TOF-MS); the levels of α2–3-linked sialic acids on PSA illustrated great potential in discriminating malignant from benign conditions, thereby improving prostate cancer diagnosis [88]. During the early stages of an acutephase immune response, the SLX levels of α-1-acid glycoprotein increase significantly, which continues throughout the whole acute phase immune response [206–208]
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