Gastric cancer is the fifth most common cancer in terms of incidence worldwide. The incidence of this cancer is decreasing, however it still causes about 800,000 deaths per year (2020). This is mainly due to the late diagnosis of the disease at symptomatic stages related to the lack of effective screening methods. Currently, the best screening tool is the detection of pepsinogen I and II levels in the circulation with a sensitivity of 66,7 - 84,6% and a specificity of 73,5 - 87,1%. Therefore, there is a need for an improvement in the diagnosis of early stage gastric cancer. The European Commission has identified the lack of an acceptable and non-invasive screening tool for this cancer and initiated research programmes aiming at the development of novel screening methods. Over the last decade the studies on human volatilomics have provided sufficient proof that volatilome is a powerful tool capable of providing novel biomarkers for medical diagnosis. The volatilome is a compilation of volatile organic compounds (VOCs) in human organism. VOCs form specific biochemical signatures that can be altered by abnormal body biochemistry and exploited in medical diagnosis. Therefore, the analysis of VOC fingerprints in different bodily fluids and tissues provides a unique opportunity to screen for various diseases, including cancer. Breath analysis holds, in this context, a distinguish status as respiratory VOCs quickly reflect physiological processes occurring in the human body. In addition, breath analysis provides non-invasive, rapid and early information on disease-related processes occurring in the body. Volatilomic approach has been used extensively over the last decade to detect and classify gastric cancer via human breath analysis. A number of recent studies in different geographic locations involving various e-noses have yielded very promising results. E-noses combined with a pattern recognition are able to discriminate gastric cancer patients from other patients and controls with a sensitivity and specificity ranging from 71 to 100% and 79 to 98%, respectively. Thus, the analysis of volatile organic compounds in human breath can potentially be used to screen for gastric cancer. However, the above approach has some limitations that directly affect the application of breath tests in clinical environment. The main unresolved problem is the uncertain identification of potential biomarkers of gastric cancer, as well as the understanding of their origin and the metabolic processes underlying their altered expression in the human body. The ambition of the present dissertation is to gain new knowledge about volatile biomarkers of gastric cancer, which could potentially be used for screening of this cancer via breath gas analysis. This knowledge is expected to provide a better understanding of the biological mechanisms undelying changes in VOC signatures in patients with gastric cancer and facilitate the development and optimization of a suitable chemical analyzer for the early diagnosis of this desease. The dissertation employs a hybrid volatilomics approach that combines the chemical information obtained from different body fluids and tissues. Such an approach provides more complementary information, and more robust identification of biomarkers with a high diagnostic potential.
The hybrid volatilomic approach applied within this dissertation involved chemical information from 3 sources: (i) VOC signatures of selected gastric cancer cell lines, (ii) VOC signatures of gastric cancer and healthy tissues and (iii) VOC signatures of gastric juice obtained from patients and controls. Experimental studies were based on gas chromatography coupled with mass spectrometry and also two preconcentration methods: headspace solid phase microextraction (HS-SPME) and headspace needle trap extraction (HS-NTE). The laboratory research was carried out in cooperation with international experts in oncology and gastric cancer diagnostics (University of Latvia), nanotechnology and non-invasive medical diagnostics (TECHNION Israel Institute of Technology), chemical analysis of exhaled air (University of Innsbruck), and cancer centers from Ukraine (National Cancer Institute of Ukraine), Colombia (University Hospital San Ignacio) and Brazil (A. C. Camargo Cancer Center). As the results a library of potential volatile biomarkers of gastric cancer has been built.
Jan 10, 2024
Jan 10, 2024