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Breath Analysis for Early Detection of Malignant Pleural Mesothelioma: Volatile Organic Compounds (VOCs) Determination and Possible Biochemical Pathways

Malignant pleural mesothelioma (MPM) is a rare neoplasm, mainly caused by asbestos exposure, with a high mortality rate. The management of patients with MPM is controversial due to a long latency period between exposure and diagnosis and because of non-specific symptoms generally appearing at advanc...

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Autores principales: Di Gilio, Alessia, Catino, Annamaria, Lombardi, Angela, Palmisani, Jolanda, Facchini, Laura, Mongelli, Teresa, Varesano, Niccolò, Bellotti, Roberto, Galetta, Domenico, de Gennaro, Gianluigi, Tangaro, Sabina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7280981/
https://www.ncbi.nlm.nih.gov/pubmed/32429446
http://dx.doi.org/10.3390/cancers12051262
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author Di Gilio, Alessia
Catino, Annamaria
Lombardi, Angela
Palmisani, Jolanda
Facchini, Laura
Mongelli, Teresa
Varesano, Niccolò
Bellotti, Roberto
Galetta, Domenico
de Gennaro, Gianluigi
Tangaro, Sabina
author_facet Di Gilio, Alessia
Catino, Annamaria
Lombardi, Angela
Palmisani, Jolanda
Facchini, Laura
Mongelli, Teresa
Varesano, Niccolò
Bellotti, Roberto
Galetta, Domenico
de Gennaro, Gianluigi
Tangaro, Sabina
author_sort Di Gilio, Alessia
collection PubMed
description Malignant pleural mesothelioma (MPM) is a rare neoplasm, mainly caused by asbestos exposure, with a high mortality rate. The management of patients with MPM is controversial due to a long latency period between exposure and diagnosis and because of non-specific symptoms generally appearing at advanced stage of the disease. Breath analysis, aimed at the identification of diagnostic Volatile Organic Compounds (VOCs) pattern in exhaled breath, is believed to improve early detection of MPM. Therefore, in this study, breath samples from 14 MPM patients and 20 healthy controls (HC) were collected and analyzed by Thermal Desorption-Gas Chromatography-Mass Spectrometry (TD-GC/MS). Nonparametric test allowed to identify the most weighting variables to discriminate between MPM and HC breath samples and multivariate statistics were applied. Considering that MPM is an aggressive neoplasm leading to a late diagnosis and thus the recruitment of patients is very difficult, a promising data mining approach was developed and validated in order to discriminate between MPM patients and healthy controls, even if no large population data are available. Three different machine learning algorithms were applied to perform the classification task with a leave-one-out cross-validation approach, leading to remarkable results (Area Under Curve AUC = 93%). Ten VOCs, such as ketones, alkanes and methylate derivates, as well as hydrocarbons, were able to discriminate between MPM patients and healthy controls and for each compound which resulted diagnostic for MPM, the metabolic pathway was studied in order to identify the link between VOC and the neoplasm. Moreover, five breath samples from asymptomatic asbestos-exposed persons (AEx) were exploratively analyzed, processed and tested by the validated statistical method as blinded samples in order to evaluate the performance for the early recognition of patients affected by MPM among asbestos-exposed persons. Good agreement was found between the information obtained by gold-standard diagnostic methods such as computed tomography CT and model output.
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spelling pubmed-72809812020-06-15 Breath Analysis for Early Detection of Malignant Pleural Mesothelioma: Volatile Organic Compounds (VOCs) Determination and Possible Biochemical Pathways Di Gilio, Alessia Catino, Annamaria Lombardi, Angela Palmisani, Jolanda Facchini, Laura Mongelli, Teresa Varesano, Niccolò Bellotti, Roberto Galetta, Domenico de Gennaro, Gianluigi Tangaro, Sabina Cancers (Basel) Article Malignant pleural mesothelioma (MPM) is a rare neoplasm, mainly caused by asbestos exposure, with a high mortality rate. The management of patients with MPM is controversial due to a long latency period between exposure and diagnosis and because of non-specific symptoms generally appearing at advanced stage of the disease. Breath analysis, aimed at the identification of diagnostic Volatile Organic Compounds (VOCs) pattern in exhaled breath, is believed to improve early detection of MPM. Therefore, in this study, breath samples from 14 MPM patients and 20 healthy controls (HC) were collected and analyzed by Thermal Desorption-Gas Chromatography-Mass Spectrometry (TD-GC/MS). Nonparametric test allowed to identify the most weighting variables to discriminate between MPM and HC breath samples and multivariate statistics were applied. Considering that MPM is an aggressive neoplasm leading to a late diagnosis and thus the recruitment of patients is very difficult, a promising data mining approach was developed and validated in order to discriminate between MPM patients and healthy controls, even if no large population data are available. Three different machine learning algorithms were applied to perform the classification task with a leave-one-out cross-validation approach, leading to remarkable results (Area Under Curve AUC = 93%). Ten VOCs, such as ketones, alkanes and methylate derivates, as well as hydrocarbons, were able to discriminate between MPM patients and healthy controls and for each compound which resulted diagnostic for MPM, the metabolic pathway was studied in order to identify the link between VOC and the neoplasm. Moreover, five breath samples from asymptomatic asbestos-exposed persons (AEx) were exploratively analyzed, processed and tested by the validated statistical method as blinded samples in order to evaluate the performance for the early recognition of patients affected by MPM among asbestos-exposed persons. Good agreement was found between the information obtained by gold-standard diagnostic methods such as computed tomography CT and model output. MDPI 2020-05-16 /pmc/articles/PMC7280981/ /pubmed/32429446 http://dx.doi.org/10.3390/cancers12051262 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Di Gilio, Alessia
Catino, Annamaria
Lombardi, Angela
Palmisani, Jolanda
Facchini, Laura
Mongelli, Teresa
Varesano, Niccolò
Bellotti, Roberto
Galetta, Domenico
de Gennaro, Gianluigi
Tangaro, Sabina
Breath Analysis for Early Detection of Malignant Pleural Mesothelioma: Volatile Organic Compounds (VOCs) Determination and Possible Biochemical Pathways
title Breath Analysis for Early Detection of Malignant Pleural Mesothelioma: Volatile Organic Compounds (VOCs) Determination and Possible Biochemical Pathways
title_full Breath Analysis for Early Detection of Malignant Pleural Mesothelioma: Volatile Organic Compounds (VOCs) Determination and Possible Biochemical Pathways
title_fullStr Breath Analysis for Early Detection of Malignant Pleural Mesothelioma: Volatile Organic Compounds (VOCs) Determination and Possible Biochemical Pathways
title_full_unstemmed Breath Analysis for Early Detection of Malignant Pleural Mesothelioma: Volatile Organic Compounds (VOCs) Determination and Possible Biochemical Pathways
title_short Breath Analysis for Early Detection of Malignant Pleural Mesothelioma: Volatile Organic Compounds (VOCs) Determination and Possible Biochemical Pathways
title_sort breath analysis for early detection of malignant pleural mesothelioma: volatile organic compounds (vocs) determination and possible biochemical pathways
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7280981/
https://www.ncbi.nlm.nih.gov/pubmed/32429446
http://dx.doi.org/10.3390/cancers12051262
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