Breath biomarkers could aid early detection, helping to improve long term survival
Esophageal and stomach cancers are amongst the most commonly occurring cancers with 456,000 and 952,000 new cases respectively diagnosed globally in 2012 . Early stage
To understand the breath composition of esophageal-gastric cancer patients Sung Tong-Chin et al.  collected breath using the ReCIVA Breath Sampler. By taking advantage of the ReCIVA Breath Sampler’s ability to collect four technical replicates during a single breath collect, they were able to analyze breath using multiple mass spectrometry approaches, thus achieving detailed breath volatile organic compound (VOC) structural data. Figure 1 shows the relative intensity of VOCs, across a population of 21 patients with esophageal-gastric cancer. This provides a useful basis for designing and interpreting future studies aiming to find early stage breath disease biomarkers in the patient population.
|Figure 1. Box and whisker plot of the relative intensity of VOC composition in
In Adam et al. , members of the same research group at Imperial College London compared volatile fatty acids (VFAs) – a particular group of VOCs – in breath from healthy individuals and esophageal-gastric cancer patients. They used the ReCIVA Breath Sampler to collect mixed breath samples from all participants and to investigate differences in VFA concentrations. The samples were analyzed using thermal desorption gas chromatography mass spectrometry (TD-GC-MS). The results show significant increases in acetic acid, butyric acid and pentanoic acid levels in breath from cancer patients. The team also collected air samples from within the lungs (isolated bronchial breath) and stomachs (gastric endoluminal) for some subjects. Comparing the levels of VFAs in these different locations shows that levels are much higher in the stomach than in the breath, but there is little difference between sampling isolated bronchial breath and mixed breath.
|Table 1: Median values of peak areas (counts rate x103) of volatile fatty acids in different aerodigestive compartments between patients and controls|
Adam et al. provide a proof of principle for detection of esophageal-gastric cancer using exhaled breath analysis, highlighting the potential for Breath Biopsy to be applied in the detection of esophagogastric cancer. However, these comparisons are based on sampling just 43 individuals and do not focus specifically on early stage cancers. More research is needed to demonstrate a conclusive link between exhaled VFA levels and early stage cancer. There are also many other candidate VOCs that could be investigated as more sensitive or effective indicators of esophageal-gastric cancer that might enable effective early detection in the patient population.
These findings suggest that VFAs find their way into breath through the blood and not through the airways directly. They also add to the evidence supporting a marked change in fatty acid metabolism within cancer cells resulting in a notable increase in VFA production. In addition, the similarities between isolated bronchial breath and mixed breath samples support the value of mixed breath sampling in non-invasive cancer detection, without the need for complex devices for alveolar sampling.
 Ferlay, J. et al. GLOBOCAN 2012v1.1, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 http://globocan.iarc.fr (2014).
 Sung-Tong Chin et al., Cross-platform mass spectrometry annotation in breathomics of oesophageal-gastric cancer, Sci. Rep., 8, 5139 (2018).
 Adam et al., Mass spectrometry analysis of mixed breath, isolated bronchial breath and gastric endoluminal volatile fatty acids in oesophagogastric cancer, Anal. Chem. 91(5), 3740-3746 (2019). https://dx.doi.org/10.1021/acs.analchem.9b00148