Cancer biomarker discovery using selected ion flow tube mass spectrometry

Abstract

Lung cancer is one of the most common types of neoplasm and is a leading cause of death in Canada. Accurate early diagnosis is key to the effective treatment of the disease, however the current means to do so, such as Computed Tomography diagnostic imaging, are costly, invasive, and not practical for routine use. The detection of volatile cancer biomarkers in breath represents an attractive non-invasive means to diagnose the disease. It is unclear, however, which, if any, breath chemicals have diagnostic utility. In this thesis I used Selected Ion Flow Tube Mass Spectrometry (SIFT-MS), a trace gas analytic method to (a) identify potential volatile cancer biomarkers in blood, and (b) investigate whether these markers are present in breath. Potential biomarkers were identified by comparing products ions formed in the reaction between hydronium (H3O+) and nitronium (NO+) precursor ions and trace gases present in the headspace of plasma obtained from patients with breast cancer, colorectal or lung cancer, and healthy controls. Using this approach product ions of interest were identified which derive from a wide range of chemical classes including aldehydes, acids, alcohols and sulphides, including some which have been identified previously by other investigators. Many of these ions could be quantified in the breath of healthy controls and therefore be suitable for quantification by breath analysis. The production rate of most of these ions was, however, poorly correlated between those formed in the reactions between nasal breath and those formed in reactions with blood headspace, even when using in samples collected and analysed simultaneously from the same participants. The lack of correlation suggests that the breath trace gases from which these product ions are formed are not dependent on the blood concentration of the same gas, but likely derive mainly from the airways. As such while my data suggest that cancer biomarkers may be found in the bloodstream, breath analysis is not a suitable means to non-invasively detect these cancer markers, in particular cancers of tissues other than those found in the airway. On the other hand, my data suggests that the detection of airway disease, including that of lung cancer, may be suitable candidates for the diagnosis and/or screening using breath analysis.