Volatile organic compounds as breathomic viomarkers of malignant mesothelioma

Malignant pleural mesothelioma (MPM) is an aggressive and incurable cancer with an extremely poor 5-year survival rate. The majority of MPM cases are associated with past exposure to asbestos and the most common route of exposure is through occupation. Current diagnostic methods are invasive, leading to patient discomfort, and often are not capable of diagnosing MPM in the early stages. Most MPM patients are therefore diagnosed at a late stage when treatment options are limited, and overall survival is approximately 12 months. Novel diagnostic methods are required to reliably detect MPM at an early stage, where prognosis and treatment options can be improved. Analysis of volatile organic compounds (VOCs) in exhaled breath has shown the potential to identify MPM patients and therefore provide a non-invasive method of detection through a diagnostic breath test. A VOC based breath test for MPM diagnosis has not yet reached clinical practice. The aim of the current project was to explore in vitro VOC analysis within mesothelioma to identify candidate VOC biomarkers at a cellular level and accelerate MPM breath analysis. To achieve this aim, a gas chromatography-mass spectrometry (GC-MS) method was developed to identify VOCs released from cell cultures. GC-MS was used to detect and identify VOCs in the headspace gas of a panel of MPM and control cell lines, statistical analysis associated specific compounds with MPM. The GC-MS methodology was then used to identify changes in VOC profiles caused by mutations in the BAP1 gene, the most commonly mutated gene in MPM. Finally, GC-MS was used to analyse the headspace gas of MPM cell xenografts generated using a chorioallantoic membrane (CAM) model. This was the first time hat VOCs had been identified from CAM xenografts and represents a progression of pre-clinical VOC analysis methods. The current results show that VOC analysis models are important tools in the progression of MPM breath analysis. Further development of these findings has the potential to lead to a clinical impact and the development of a diagnostic breath test within MPM.