What is it about?

Aberrant glycosylation on glycoproteins that are either presented on the surface or secreted by cancer cells is a potential source of disease biomarkers and provides insights into disease pathogenesis. N-Glycans of the total serum glycoproteins from advanced breast cancer patients and healthy individuals were sequenced by HPLC with fluorescence detection coupled with exoglycosidase digestions and mass spectrometry. Preliminary findings suggest that specific glycans and glycoforms of proteins may be candidates for improved markers in the monitoring of breast cancer progression.

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Why is it important?

This study sequenced the N-glycans of serum proteins from advanced breast cancer patients using a combination of NP- and WAX-HPLC, exoglycosidase digestion arrays, and mass spectrometry techniques. This has highlighted a significant increase in sialylation and changes in fucosylation in breast cancer patient sera compared to that from controls. More importantly, elevated levels of the sLex-carrying triantennary structure, A3FG1, derived from the monofucosylated trisialylated triantennary N-glycan (A3FG3S3), were detected in the serum of patients. The study found an increase of more than 2-fold in advanced breast cancer. In a retrospective study, the researchers compared levels of this glycan marker to CA 15-3 at initial diagnosis and metastasis and observed that it serves as a more sensitive tool compared to CA 15-3 for detecting metastasis and breast cancer progression in general. This preliminary study has highlighted a specific glycan marker and a quantitative approach to monitor its level in breast cancer patients which the researchers propose would be most beneficial as a tool in personalized medicine.

Perspectives

Breast cancer is amongst the most prevalent cancers in the world and accounts for the highest number of cancer-related deaths among women worldwide. Each year, more than 1.1 million new cases are diagnosed with over 400,000 deaths recorded. As in any other malignancy, there is an urgent need for non-invasive markers for diagnostics, evaluating prognosis and monitoring treatment. The most commonly used markers for breast cancer are CA 15-3 and carcinoembryonic antigen (CEA). CA 15-3, however, has low specificity and sensitivity for breast cancer, two important criteria for a biomarker. Therefore, it is often measured together with CEA and only recommended for determining prognosis and monitoring patients. Aberrant glycosylation is an established hallmark of cancer and extensive studies have highlighted the role of glycan structures in cancer development.

Dr Umi M Abd Hamid
Universiti Teknologi MARA

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This page is a summary of: A strategy to reveal potential glycan markers from serum glycoproteins associated with breast cancer progression, Glycobiology, August 2008, Oxford University Press (OUP),
DOI: 10.1093/glycob/cwn095.
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