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      Investigation of different approaches for exhaled breath and tumor tissue analyses to identify lung cancer biomarkers

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          Abstract

          Development of early noninvasive methods for lung cancer diagnosis is among the most promising technologies, especially using exhaled breath as an object of analysis. Simple sample collection combined with easy and quick sample preparation, as well as the long-term stability of the samples, make it an ideal choice for routine analysis. The conditions of exhaled breath analysis by preconcentrating volatile organic compounds (VOCs) in sorbent tubes, two-stage thermal desorption and gas-chromatographic determination with flame-ionization detection have been optimized. These conditions were applied to estimate differences in exhaled breath VOC profiles of lung cancer patients and healthy volunteers. The combination of statistical methods was used to evaluate the ability of VOCs and their ratios to classify lung cancer patients and healthy volunteers. The performance of diagnostic models on the test data set was greater than 90 % for both VOC peak areas and their ratios. Some of the exhaled breath samples were analyzed using gas chromatography coupled with mass spectrometry (GC-MS) to identify VOCs present in exhaled breath at lower concentration levels. To confirm the endogenous origin of VOCs found in exhaled breath, GC-MS analysis of tumor tissues was conducted. Some of the VOCs identified in exhaled breath were found in tumor tissues, but their frequency of occurrence was significantly lower than in the case of exhaled breath.

          Abstract

          Analytical chemistry; Biomedical engineering; Cancer research; volatile organic compounds, exhaled breath analysis, tumor tissue analysis, lung cancer, thermal desorption, GC-FID, GC-MS

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          Most cited references39

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          Volatile organic compounds of lung cancer and possible biochemical pathways.

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            Volatile organic compounds in breath as markers of lung cancer: a cross-sectional study.

            Many volatile organic compounds (VOCs), principally alkanes and benzene derivatives, have been identified in breath from patients with lung cancer. We investigated whether a combination of VOCs could identify such patients. We collected breath samples from 108 patients with an abnormal chest radiograph who were scheduled for bronchoscopy. The samples were collected with a portable apparatus, then assayed by gas chromatography and mass spectroscopy. The alveolar gradient of each breath VOC, the difference between the amount in breath and in air, was calculated. Forward stepwise discriminant analysis was used to identify VOCs that discriminated between patients with and without lung cancer. Lung cancer was confirmed histologically in 60 patients. A combination of 22 breath VOCs, predominantly alkanes, alkane derivatives, and benzene derivatives, discriminated between patients with and without lung cancer, regardless of stage (all p<0.0003). For stage 1 lung cancer, the 22 VOCs had 100% sensitivity and 81.3% specificity. Cross-validation of the combination correctly predicted the diagnosis in 71.7% patients with lung cancer and 66.7% of those without lung cancer. In patients with an abnormal chest radiograph, a combination of 22 VOCs in breath samples distinguished between patients with and without lung cancer. Prospective studies are needed to confirm the usefulness of breath VOCs for detecting lung cancer in the general population.
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              Detection of lung, breast, colorectal, and prostate cancers from exhaled breath using a single array of nanosensors

              Background: Tumour growth is accompanied by gene and/or protein changes that may lead to peroxidation of the cell membrane species and, hence, to the emission of volatile organic compounds (VOCs). In this study, we investigated the ability of a nanosensor array to discriminate between breath VOCs that characterise healthy states and the most widespread cancer states in the developed world: lung, breast, colorectal, and prostate cancers. Methods: Exhaled alveolar breath was collected from 177 volunteers aged 20–75 years (patients with lung, colon, breast, and prostate cancers and healthy controls). Breath from cancerous subjects was collected before any treatment. The healthy population was healthy according to subjective patient's data. The breath of volunteers was examined by a tailor-made array of cross-reactive nanosensors based on organically functionalised gold nanoparticles and gas chromatography linked to the mass spectrometry technique (GC-MS). Results: The results showed that the nanosensor array could differentiate between ‘healthy' and ‘cancerous' breath, and, furthermore, between the breath of patients having different cancer types. Moreover, the nanosensor array could distinguish between the breath patterns of different cancers in the same statistical analysis, irrespective of age, gender, lifestyle, and other confounding factors. The GC-MS results showed that each cancer could have a unique pattern of VOCs, when compared with healthy states, but not when compared with other cancer types. Conclusions: The reported results could lead to the development of an inexpensive, easy-to-use, portable, non-invasive tool that overcomes many of the deficiencies associated with the currently available diagnostic methods for cancer.

                Author and article information

                Contributors
                Journal
                Heliyon
                Heliyon
                Heliyon
                Elsevier
                2405-8440
                17 June 2020
                June 2020
                17 June 2020
                : 6
                : 6
                : e04224
                Affiliations
                [a ]Department of Analytical Chemistry, Kuban State University, Stavropol'skaya St. 149, Krasnodar, 350040, Russia
                [b ]Research Institute – Regional Clinical Hospital № 1 n.a. Prof. S.V. Ochapovsky, 1 May St. 167, Krasnodar, 350086, Russia
                Author notes
                []Corresponding author. elina.gashimova@ 123456yandex.ru
                Article
                S2405-8440(20)31068-9 e04224
                10.1016/j.heliyon.2020.e04224
                7305397
                32577579
                3b1870c9-6ea5-4275-9298-90c5e4f3118c
                © 2020 The Author(s)

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 20 February 2020
                : 15 May 2020
                : 11 June 2020
                Categories
                Article

                analytical chemistry,biomedical engineering,cancer research,volatile organic compounds,exhaled breath analysis,tumor tissue analysis,lung cancer,thermal desorption,gc-fid,gc-ms

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