Identifying biomarkers to predict the biological behaviour of canine cutaneous mast cell tumours

SF600 Veterinary Medicine

Macfarlane, Michael John ; Morris, Joanna S.

University:University of Glasgow

Department:School of Veterinary Medicine

关键词: Veterinary oncology, oncology, mast cell tumour, biomarkers, proteomics.;   

Others  :  http://theses.gla.ac.uk/30635/1/2018macfarlanemvm.pdf

来源: University of Glasgow

【 摘 要 】

This thesis aimed to identify biomarkers which could be used to determine the biological behaviour of canine mast cell tumours. The rationale for this was that there is a relative paucity of objective biomarkers, which can be established without the need to perform an act of surgery. In order to do this, the potential array of biomarkers available were reviewed. It was considered that markers attainable by interrogation of a blood sample may be most appropriate to fulfil the identified need. After positive results in human oncology, the first analyses focused on the relationships between routinely measured parameters, both proteins (the albumin to globulin ratio) and leukocytes (the neutrophil to lymphocyte ratio). Blood samples were taken from dogs with mast cell tumours prior to any treatment intervention. The neutrophil to lymphocyte ratio was identified as a biomarker which could identify canine mast cell tumours with an aggressive biological behaviour. Building a hypothesis from results in both veterinary and human oncology it was thought that further analysis of the serum proteome could identify further biomarkers of interest. Using the same blood samples, one-dimensional serum protein electrophoresis identified that dogs with biologically aggressive mast cell tumours had more significantly increased α-2 protein concentrations than those with low grade mast cell tumours.In an attempt to identify which specific proteins were responsible for changes in the proteome between dogs with mast cell tumours and also when compared to health control dogs, two dimensional serum protein electrophoresis was then performed. Twelve proteins were identified in dogs with aggressive mast cell tumours and not in healthy controls. Some of these proteins are acute phase proteins, reflecting the inflammatory nature of this neoplasm. Others are protease inhibitors which may have a role in tumour pathogenesis. This research has identified biomarkers, which with further validation could have a role in identifying tumours likely to have a severe effect on dogs’ quality of life and allow prompt treatment. It has also identified areas for future research.