Mass-Spectrometry Analysis of Mixed-Breath, Isolated-Bronchial-Breath, and Gastric-Endoluminal-Air Volatile Fatty Acids in Esophagogastric Cancer

Abstract

A noninvasive breath test has the potential to improve survival from esophagogastric cancer by facilitating earlier detection. This study aimed to investigate the production of target volatile fatty acids (VFAs) in esophagogastric cancer through analysis of the ex vivo headspace above underivatized tissues and in vivo analysis within defined anatomical compartments, including analysis of mixed breath, isolated bronchial breath, and gastricendoluminal air. VFAs were measured by PTR-ToF-MS and GC-MS. Levels of VFAs (acetic, butyric, pentanoic, and hexanoic acids) and acetone were elevated in ex vivo experiments in the headspace above esophagogastric cancer compared with the levels in samples from control subjects with morphologically normal and benign conditions of the upper gastrointestinal tract. In 25 patients with esophagogastric cancer and 20 control subjects, receiver-operating-characteristic analysis for the cancer-specific VFAs butyric acid (P < 0.001) and pentatonic acid (P = 0.005) within in vivo gastric-endoluminal air gave an area under the curve of 0.80 (95% confidence interval of 0.65 to 0.93, P = 0.01). Compared with mixed-and bronchial-breath samples, all examined VFAs were found in highest concentrations within esophagogastric-endoluminal air. In addition, VFAs were higher in all samples derived from cancer patients compared with in the controls. Equivalence of VFA levels within the mixed and bronchial breath of cancer patients suggests that their origin within breath is principally derived from the lungs and, by inference, from the systemic circulation as opposed to direct passage from the upper gastrointestinal tract. These findings highlight the potential to utilize VFAs for endoluminal-gas biopsies and noninvasive mixed-exhaled-breath testing for esophagogastric-cancer detection.

Diagnostic Application of Volatile Organic Compounds as Potential Biomarkers for Detecting Digestive Neoplasia: A Systematic Review

“…The analysis of the breath samples was done by gas chromatography coupled with mass spectrometry (GC-MS) [ 11 , 13 , 20 , 21 , 22 , 23 ], with solid phase microextraction (SPME), [ 14 , 18 , 22 , 25 ] or with proton-transfer-reaction time-of-flight mass spectrometry (PTR-ToF-MS), selected ion flow tube mass spectrometry (SIFT-MS) [ 15 ], proton reaction mass spectrometry (PTR-MS) [ 16 ], or an array of nanosensors [ 22 ]. GC-MS retrofitted with electron ionization (EI) [ 10 ] or retrofitted with positive chemical ionization (PCI) [ 10 , 24 ].…”

“…The collection of exhaled breath was done in containers of 500 mL to 3 L [ 11 , 14 ], but oral cavity air, 20 mL, collected in headspace vials, was also analyzed [ 13 ]. The VOCs concentration levels in breath samples were compared to that in the mixed breath with headspace concentrations, bronchial breath, gastric-endoluminal air [ 14 ], with the highest concentrations being in the gastric-endoluminal air [ 14 ].…”

Feasibility and acceptability of breath research in primary care: a prospective, cross-sectional, observational study

“…Once released into the systemic circulation, VOCs may travel to the lungs where they are excreted in exhaled breath. 10 A systematic review of breath testing for cancer identified distinctive VOCs signals for different tumour sites with pooled sensitivity and specificity of 79% and 89%, respectively (including lung, breast, gastrointestinal, head and neck, prostate and gynaecological tumours). 11 Studies of different gastrointestinal tumour sites also showed different VOC biomarkers for oesophagogastric, pancreatic and colorectal cancers, providing the opportunity for a single breath test to diagnose different cancers based on their unique VOC signature, in a similar way to a single blood draw being used to assess for multiple diseases.…”

The Translational Status of Cancer Liquid Biopsies

“…A discriminant function analysis of breath VOC patterns could discriminate CRC vs healthy controls with 85% sensitivity and a 94% specificity (N = 209) [376]. Two recently published studies shown that VOCs have the potential to discriminate esophagogastric cancer patients from heathy controls [377,378]. Another study shows that VOCs can be used for early detection of pancreatic cancer [379].…”