Mina Adam (Presenter)
Imperial College London
Bio: I joined Professor George Hanna and Professor Julian Marchesi’s research group in November 2015 as a clinical PhD Research Fellow at Imperial College London. I completed my undergraduate medical education (MBBCH) honours degree at Cairo University in 2010. In 2013, I commenced my postgraduate specialist residency program in General and Gastrointestinal Oncology Surgery. This enabled me to accomplish my Master’s degree and commence my research. My current work is centred on the influence of the microbiome and its effect on volatile organic compounds excreted from human gastric mucosal tissue samples using different mass spectrometry platforms.
Authorship: Mina Adam (1), Sacheen Kumar (1), Andrea Romano (1), George B Hanna (1)
(1) Imperial College London, London, UK.
| Short Abstract The detection and quantification of Volatile Organic Compounds (VOCs) has great potential in terms of disease diagnosis and measuring physiological response to treatment. In this study, Proton-Transfer-Reaction Time-Of-Flight Mass Spectrometry (PTR-TOF-MS) has been utilised for the identification of VOCs in gastric tissue samples from patients with oesphago-gastric cancer and those with healthy stomachs. A total of 41 compounds have been investigated Six VOCs including hexanoic acid, butyric acid, phenol, hexanal, nonanal and isoprene were found at higher concentrations in in cancer patients compared to non-cancer controls; these VOCs have been observed in a previous study at increased concentrations in the exhaled breath of oesophago-gastric cancer patients The preliminary results demonstrate that specific VOCs may arise directly from tissue and provide evidence for disease profiling. |
Long Abstract
Introduction
Worldwide, there are an estimated 482,300 new cases of oesophago-gastric cancer cases per year. It affects nearly one million people per year and is responsible for around 10% of total cancer deaths globally1. The prognosis of esophago-gastric cancer is poor in Western countries as a result of the paucity of alarm symptoms in early stages of the disease; this results in late clinical presentation and associated delays in the institution of treatment2. Overall, 5-year survival rates also vary geographically with better oncological outcomes in the Far East in part due to the existence of endoscopic or radiological screening programmes that facilitate early detection of cancer3. The development of non-invasive, accurate biomarkers to determine oesophago-gastric cancer risk could help facilitate earlier diagnosis and potentially improve patient survival.
VOCs emitted from human body have been of interest to researchers since the time of Hippocrates. The identification, characterization and accurate quantification of VOCs from human samples remains challenging given the complexity of biological matrices. Several mass spectrometry techniques have been employed for the identification of VOCs, with Proton-Transfer-Reaction Time-Of-Flight Mass Spectrometry (PTR-TOF-MS) representing one of the newer methods for real time quantification of VOCs. Previous studies have identified VOCs of interest in the gastric content, urine and exhaled breath of patients with oesophago-gastric cancer4. In this study, mass spectrometric analysis of gastric mucosa has been undertaken to evaluate if these VOCs are directly emitted from cancer tissue.
Methods
Patients referred with upper gastro-intestinal symptoms are commonly referred for an oesophago-gastro-duodenoscopy (OGD) by their physician. An OGD is a routinely performed camera test in which the upper gastro-intestinal tract is directly visualized. Patients with a biopsy-confirmed oesophag-gastric cancer were included in the cancer cohort. Patients who had a normal OGD test and were confirmed as H. pylori negative were included in the “healthy” cohort group.
All gastric tissue samples were taken by endoscopic biopsy from patients undergoing OGD. Samples were immediately snap frozen in liquid nitrogen and stored at -80oC until analyzed. Prior to analysis, batches of frozen tissue samples (each~ 10mg_ were left to thaw and then transferred into 20ml headspace screw-capped vials. Each tissue sample was cut into half to allow for analysis utilising 2 different precursor ions (H3O+, NO+). All samples were kept at room temperature for 30minutes prior to analysis. The septum of the vial was pierced to allow for the placement of the PTR probe with clean air given by an air pump with a flow rate of 40ml/min to avoid vacuum in the vials created by different parts of the instrument.
Selected precursor ions, specifically H3O+ and NO+, were used to ionize the trace gases in the headspace of tissue samples. PTR-TOF-MS provides a means for separating ions according to their mass/charge ratio, connecting it to a sensitive ion detector and associated data acquisition electronics to achieve the requisite overall detection sensitivity. Real-time quantification was achieved producing absolute concentration of trace and volatile compounds at sub parts-per-billion by-volume (ppbv). Mass calibrations, peak data and primary ion settings was used for each ion precursor, which subsequently generated specific data tables with the use of the PTR-TOF-MS automation center software. Supervised and unsupervised statistical modelling was performed with incorporation of clinical metadata.
Results
In total, 41 VOCs in both cancer and healthy gastric mucosa samples were analysed using PTR-TOF-MS. Samples were classified into cancer and healthy groups following histopathological confirmation. Univariate statistical analysis demonstrated that the concentrations of hexanoic acid, butyric acid, hexanal, nonanal, phenol and isoprene were increased in oesophago-gastric cancer tissue compared to healthy controls. The same VOCs have been observed in a previous study at increased concentrations in the exhaled breath of oesophago-gastric cancer patients.
Conclusions & Discussion
This is the first study to employ Proton-Transfer-Reaction Time-Of-Flight Mass Spectrometry for analysis of VOCs in tissue from oesophago-gastric cancer patients. The results obtained indicate that cancer-specific VOCs are directly emitted by from tissue without the need for derivatisation. Moreover, there is a possibility to create a cancer-specific VOC fingerprint that could be used for disease diagnostics. The preliminary results demonstrate that oesophago-gastric cancer-specific VOCs may arise directly from tissue and provide further evidence for the development VOC profiling for disease diagnosis.
References & Acknowledgements:
1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–90.
2. Arvanitakis C, Nikopoulos A, Giannoulis E, Theoharidis A, Georgilas V, Fotiou H, et al. The impact of early or late diagnosis on patient survival in gastric cancer in Greece. Hepatogastroenterology. 1992 Aug;39(4):355–7.
3. Miyamoto A, Kuriyama S, Nishino Y, Tsubono Y, Nakaya N, Ohmori K, et al. Lower risk of death from gastric cancer among participants of gastric cancer screening in Japan: A population-based cohort study. Prev Med (Baltim). 2007;44(1):12–9.
4. Kumar S, Huang J, Abbassi-Ghadi N, Mackenzie HA, Veselkov KA, Hoare JM, Lovat LB, Spanel P, Smith D, Hanna GB. Mass spectrometric analysis of exhaled breath for the identification of volatile organic compound biomarkers in esophageal and gastric adenocarcinoma. Ann Surg 2015
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