Cross-platform mass spectrometry annotation in breathomics of oesophageal-gastric cancer

Abstract

Disease breathomics is gaining importance nowadays due to its usefulness as non-invasive early cancer detection. Mass spectrometry (MS) technique is often used for analysis of volatile organic compounds (VOCs) associated with cancer in the exhaled breath but a long-standing challenge is the uncertainty in mass peak annotation for potential volatile biomarkers. This work describes a cross-platform MS strategy employing selected-ion flow tube mass spectrometry (SIFT-MS), high resolution gas chromatography-mass spectrometry (GC-MS) retrofitted with electron ionisation (EI) and GC-MS retrofitted with positive chemical ionisation (PCI) as orthogonal analytical approaches in order to provide facile identification of the oxygenated VOCs from breath of cancer patients. In addition, water infusion was applied as novel efficient PCI reagent in breathomics analysis, depicting unique diagnostic ions M+ or [M-17]+ for VOC identification. Identity confirmation of breath VOCs was deduced using the proposed multi-platform workflow, which reveals variation in breath oxygenated VOC composition of oesophageal-gastric (OG) cancer patients with dominantly ketones, followed by aldehydes, alcohols, acids and phenols in decreasing order of relative abundance. Accurate VOC identification provided by cross-platform approach would be valuable for the refinement of diagnostic VOC models and the understanding of molecular drivers of VOC production.

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 ]. GC-MS is an off-line analytical technique that needs absorption devices and column calibration for the desired analytes [ 9 ], and the VOCs are identified by MS database/library matches [ 19 , 21 , 23 ].…”

“…VOCs are considered as potential biomarkers for non-invasive early cancer detection [ 2 , 10 ], as screening tools especially for high risk patients, e.g., smokers, heavy drinkers, or as post-therapeutic monitoring for recurrence occurrence [ 11 ]. We herein aimed to review the breath VOCs identified in digestive cancers.…”

Fast and noninvasive electronic nose for sniffing out COVID-19 based on exhaled breath-print recognition

“…Additionally, a few other compounds are also detected in exhaled breath (e.g., benzene, acetonitrile, diallyl sul de, allyl methyl sul de, and diallyl disul de). 18,19 It is well known that several VOCs with their speci c compositions can be utilized as noninvasive biomarkers for various respiratory diseases, including oesophageal-gastric cancer 16 , lung cancer 20 , asthma 21 , rhinovirus-induced wheeze 22 , in uenza infection in swine 23 , and tuberculosis 24 . Recent evidence indicated that COVID-19 could also be diagnosed using a VOC-based breath analysis approach by means of near-patient gas chromatography-ion mobility spectrometry (GC-IMS).…”

“…They could be detected by gas chromatography-mass spectroscopy (GC-MS) and proton transfer reaction-mass spectrometry (PTR-MS). 16,17 The most abundant VOCs from exhaled human breath are acetone, methanol, ethanol, propanol, and isoprene. Additionally, a few other compounds are also detected in exhaled breath (e.g., benzene, acetonitrile, diallyl sul de, allyl methyl sul de, and diallyl disul de).…”

Hybrid Analytical Platform Based on Field-Asymmetric Ion Mobility Spectrometry, Infrared Sensing, and Luminescence-Based Oxygen Sensing for Exhaled Breath Analysis

“…Due to the inherent complexity, it is almost impossible to comprehensively analyze breath samples with single analytical techniques. Therefore, hyphenated approaches combining a molecularly selective device (e.g., mass spectrometry (MS) [11,12,13] or ion mobility spectrometry (IMS) [14,15,16]) with preconcentration schemes (e.g., via solid-phase microextraction (SPME) or needle trap devices (NTD) [4,17,18]) and/or pre-separation strategies (e.g., via gas chromatography (GC) or multi-capillary columns (MCC) [3,14,15,16,19]) are considered the state-of-the-art for addressing trace concentrations and to reduce sample complexity. Yet, in most cases, only one type of ‘detector’ (e.g., MS or IMS) is still used, limiting the number of detectable breath analytes.…”