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Title: Alpha-1-acid glycoprotein as a potential biomarker of breast cancer in 'at risk' individuals
Author: Dewar, Emma Louise
ISNI:       0000 0004 5919 9157
Awarding Body: Edinburgh Napier University
Current Institution: Edinburgh Napier University
Date of Award: 2015
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The identification of a blood-based diagnostic biomarker for breast cancer (BC) would be particularly beneficial to those at increased risk of developing BC and could result in earlier detection which may increase survival rates due to earlier treatment. Alterations in α-1-acid glycoprotein (AGP) glycosylation levels occur during disease and this study sought to determine the diagnostic potential of AGP glycan variation in triple negative breast cancer (TNBC) compared to BC of unknown type and healthy controls as well as women at increased risk of developing BC compared to age-matched healthy controls. AGP was isolated from blood of two different sample populations using low pressure chromatography. AGP purity was confirmed using SDS-PAGE and concentration determined using spectrophotometry. Structural analysis of AGP glycan monosaccharide and oligosaccharide content was undertaken using high pH anion-exchange chromatography with pulsed amperometric detection (HPAEC-PAD). Increased AGP concentrations were observed, in comparison to their controls, in BC of unknown type, TNBC and “at-risk” samples. Quantitative alterations in monosaccharide composition were also present. N-acetylgalactosamine (GalNAc) was present in over 88% of TNBC samples and was inversely correlated with age. For the TNBC groups, GalNAc was also present at higher levels in samples of individuals with family history of BC. There was an overall increase in GlcNAc levels compared to age-matched healthy controls and GalNAc presence in 81% of “at risk” samples. Oligosaccharide analysis revealed increased branching in BC of unknown type and TNBC < 35 years of age, whereas the “normal” healthy population and TNBC >35 possessed less branching. A similar trend was observed between the “at risk” samples and the age-matched controls. These branching patterns aligned well with the corresponding monosaccharide data. Overall, this study indicated that alterations in AGP levels and glycosylation exist between TNBC compared to BC of unknown type and “normal” healthy controls as well as an “at risk” population and age-matched healthy controls. The data could underpin the development of a new diagnostic BC biomarker.
Supervisor: Smith, Kevin Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QR Microbiology