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

Alessia Di Gilio,Jolanda Palmisani,Roberto Bellotti,Domenico Galetta,Annamaria Catino,Sabina Tangaro,Angela Lombardi,Niccolò Varesano,Laura Facchini,Teresa Mongelli,Gianluigi De Gennaro

doi:10.3390/cancers12051262

Abstract

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.

Highlights

Malignant pleural mesothelioma (MPM) is a rare neoplasm mainly correlated to asbestos exposure.Asbestos mainly refers to six fibrous silicate minerals and it was widely used in building construction during the 20th century due to its strong chemical, abrasion and fire resistance [1,2]
Taking into account that MPM is a rare and aggressive neoplasm making patient recruitment difficult, this study aims to identify a distinct mesothelioma-related Volatile Organic Compounds (VOCs) profile through breath analysis by developing and validating a promising data mining approach able to discriminate between MPM patients and healthy controls, even if no large population data are available
Taking into account that MPM is a rare and aggressive neoplasm and that the recruitment of MPM patients is very difficult due to late diagnosis, this study reported a promising data mining approach which was developed and validated in order to discriminate between MPM patients and healthy controls, even if large population data are not available

Summary

Introduction

Malignant pleural mesothelioma (MPM) is a rare neoplasm mainly correlated to asbestos exposure.Asbestos mainly refers to six fibrous silicate minerals (chrysotile, amosite, crocidolite, anthophyllite, tremolite and actinolite) and it was widely used in building construction during the 20th century due to its strong chemical, abrasion and fire resistance [1,2]. Malignant pleural mesothelioma (MPM) is a rare neoplasm mainly correlated to asbestos exposure. The use of asbestos in developed countries has been banned since 2005, MPM is still a major public health issue. The reported median survival for MPM is less than 1 year, with a 5-year survival rate below 5%. This dismal prognosis is mainly due to generally late diagnosis in advanced stages, and invasive diagnostic procedures such as a tissue biopsy obtained by thoracoscopy are often necessary to discriminate benign conditions from uncertain and/or neoplastic pleural lesions

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