Abstract
Lung cancer is the leading cause of cancer deaths. Unfortunately, lung cancer is often diagnosed only when it becomes symptomatic or at an advanced stage when few treatment options are available. Hence, a diagnostic test suitable for screening widespread populations is required to enable earlier diagnosis. Analysis of exhaled breath provides a non-invasive method for early detection of lung cancer. Analysis of volatile organic compounds (VOCs) by various mass spectral techniques has identified potential biomarkers of disease. Nevertheless, the metabolic origins and the disease specificity of VOCs need further elucidation. Cell culture metabolomics can be used as a bottom-up approach to identify biomarkers of pathological conditions and can also be used to study the metabolic pathways that produce such compounds. This paper summarizes the current knowledge of lung cancer biomarkers in exhaled breath and emphasizes the critical role of cell culture conditions in determining the VOCs produced in vitro. Hypoxic culture conditions more closely mimic the conditions of cancer cell growth in vivo. We propose that since hypoxia influences cell metabolism and so potentially the VOCs that the cancer cells produce, the cell culture metabolomics projects should consider culturing cancer cells in hypoxic conditions.
Highlights
Lung cancer is one of the five most commonly diagnosed cancers and is the leading cause of cancer-related deaths throughout the world [1,2,3]
The diagnostic volatile organic compounds (VOCs) identified in these studies were mostly alkanes that showed decrease in exhaled breath compared to room air, which is believed to occur due to metabolism by cytochrome P450 mixed function oxidases that are up-regulated in cancer
Differences in the VOCs found in breath and in the headspace of cancer cell lines can be attributed to many causes such as different sampling methodology, mass spectral techniques and statistical approaches
Summary
Lung cancer is one of the five most commonly diagnosed cancers and is the leading cause of cancer-related deaths throughout the world [1,2,3]. Knowledge of all the VOCs produced by lung cancer cells should lead to a panel of diagnostic biochemical markers that can be measured. Previous studies have found poor correlations between the VOCs from cancer cells in culture and those found by breath analysis (see section 2 of this paper). In vivo cancer cells experience low oxygen or hypoxic conditions as a consequence of the diffusion limit within tissues, which has been measured to be around 150 μm [5, 6]. We summarize the current state of knowledge about biomarkers of lung cancer in exhaled breath but with an emphasis on the critical role of cell culture conditions in in vitro studies in determining the VOCs produced. Cell culture metabolomics projects should consider culturing cancer cells in hypoxic conditions
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