Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.571697
Title: Combining molecular and imaging biomarkers to optimise response prediction in oesphagogastric adenocarcinoma
Author: Bain, Gillian H.
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 2013
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Abstract:
Predicting whether patients will respond to particular treatments and identifying molecular targets for novel innovative therapies within the context of a paradigm shift towards individualised selection of therapy is a priority for translational research in oesophagogastric adenocarcinoma. Changes in tumour glucose metabolism detected early in the course of chemotherapy (14 days) by fluorodeoxyglucose-positron emission tomography (FDG-PET), has demonstrated efficacy for prediction of response and clinical benefit from chemotherapy. However, while the specificity of FDG-PET is high (95%), sensitivity is limited (50%) and ideally for clinical implementation the predictive accuracy for response (as opposed to non- response) should be improved. We hypothesised that response prediction could be optimised by combining FDG-PET with (1) molecular biomarkers (obtained from global gene expression profiling of tumour samples using an oligonucleotide microarray), (2) plasma biomarkers of cell death [Cytokeratin 18 (CK18) M30 (apoptosis) and M65 (apoptosis and necrosis) enzyme linked immunosorbent assays (ELISAs)] and (3) measures of tumour perfusion [using perfusion computed tomography (CT)]. We also hypothesised that gene expression profiling would identify potential novel therapeutic targets in metabolic non responders. A ‘predictive geneset’ for radiological response in metabolic responders was identified. A number of pathways including the adipocytokine signalling pathway were found to be over-represented in a larger predictive geneset which also separated metabolic responding tumours according to whether or not they subsequently went on to have a radiological response to chemotherapy. The genes represented from this pathway included leptin which was increased in non-responding as opposed to responding tumours. In an independent set, leptin expression was correlated with poor histopathological response a A ‘predictive geneset’ for radiological response in metabolic responders was identified. A number of pathways including the adipocytokine signalling pathway were found to be over-represented in a larger predictive geneset which also separated metabolic responding tumours according to whether or not they subsequently went on to have a radiological response to chemotherapy. The genes represented from this pathway included leptin which was increased in non-responding as opposed to responding tumours.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.571697  DOI: Not available
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