Abstract

Malignant mesothelioma (MM) is an incurable cancer. MM is often misdiagnosed, with a poor 5-year survival and limited treatment options. The discovery of endogenous volatile organic compounds (VOCs) is required in order to accelerate the development of a breath test as an alternative to conventional MM diagnosis. For the first time, this study used solid-phase microextraction and gas chromatography-mass spectrometry to identify VOCs released directly from the biphasic MM cell line MSTO-211H and the epithelioid MM cell line NCI-H28 as well as the non-malignant mesothelial cell line MET-5A. Multivariate statistical analysis showed separation between MSTO-211H, NCI-H28 and MET-5A results. 2-ethyl-1-hexanol was significantly increased in both MSTO-211H and NCI-H28 cells compared to MET-5A controls. In addition, ethyl propionate and cyclohexanol were significantly increased in MSTO-211H cells and dodecane was significantly increased in NCI-H28 cells. This is the first study reporting headspace analysis of these MM cell lines and the first to consider the effects of mesothelioma sub-type on VOC profile. Current results further highlight the potential for a diagnostic mesothelioma breath test as well as providing proof of concept for the differentiation between biphasic and epithelioid mesothelioma based on VOC profiles.

Highlights

  • Malignant mesothelioma (MM) is an extremely aggressive and incurable malignancy most commonly affecting the mesothelial cell lining of the pleura as well as other internal organs [1]

  • Chromatograms produced from Solid-phase microextraction (SPME) gas chromatography-mass spectrometry (GC-MS) of MSTO-211H, NCI-H28 and MET-5A groups appeared very similar, making it difficult to identify any observable differences in volatile organic compounds (VOCs)

  • MM breath analysis is still in its early stages— previous studies have provided a proof of concept for the identification of MM patients based on VOCs in exhaled breath

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Summary

Introduction

Malignant mesothelioma (MM) is an extremely aggressive and incurable malignancy most commonly affecting the mesothelial cell lining of the pleura as well as other internal organs [1]. Despite the regulation of asbestos which was introduced in the mid-1980s, UK MM incidence has risen in that time due to a prolonged latency period of up to 60 years since initial exposure [4]. It is difficult to identify patients at an early stage due to the prolonged latency period and non-specific signs and symptoms such as chest pains and pleural effusions, which present only in the late stages of the disease [7]. Definitive MM diagnosis must be confirmed through a chest CT scan and invasive biopsies [8] These issues highlight the requirement of a novel diagnostic method within MM; one capable of identifying patients at an earlier disease stage, differentiating between MM sub-types and avoiding invasive biopsy procedures

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