Investigating Metabolic Changes Associated with Human Oncology
Student thesis: Master's Thesis › Master of Philosophy
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Cancer is a major global health problem which, although it arises through genetic changes, has consequences which are reflected in cellular metabolism. Metabolomics is a method through which thousands of metabolites may be assessed in a high-through-put mode. Metabolomics was employed to seek out potential biomarkers for diagnosing and staging lung and gastric cancer malignancies. For lung cancer, saliva was selected as the biofluid for investigation as it is non-invasive and few salivary biomarkers have been defined Investigations for potential biomarkers for gastric tumours focused on gastric fluid which has not been explored as a biofluid in metabolomic analyses. In terms of novel biomarkers for the early diagnosis of lung cancer, 43 statistically significant (P<0.05) metabolites were identified, of which 40 met the Area Under the Curve (AUC) threshold for sensitivity and specificity (≥ 0.7) to make them of clinical interest. For staging of lung cancers 16 metabolites were found show statistically significant (P<0.05, ANOVA) difference between the stages. The gastric fluids could be separated into clusters using multivariate statistics but no biomarkers were found which were both statistically (using ANOVA) and clinically significant (as indicated by AUC). However, in terms of gaining insight into the pathways and mechanisms associated with malignancy we have found metabolites representing significant changes in methylation, inflammation, redox change and amino acid processing. These experiments were all carried out using comparatively small data sets so the studies would need to be investigated using larger cohorts from multiple hospitals and blinded. Then the potential biomarkers found in this study could be tested for their robustness and repeatability, as well as their sensitivity and specificity.
Thesis, 2.85 MB, PDF
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Thesis, 2.85 MB, PDF
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