Exhaled volatile organic compounds for diagnosis of hepatocellular carcinoma

Abstract Volatile organic compounds (VOCs) profile for diagnosis and monitoring therapeutic response of hepatocellular carcinoma (HCC) has not been well studied. We determined VOCs profile in exhaled breath of 97 HCC patients and 111 controls using gas chromatography–mass spectrometry and Support Ve...

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Main Authors: Thanikan Sukaram, Rossarin Tansawat, Terapap Apiparakoon, Thodsawit Tiyarattanachai, Sanparith Marukatat, Rungsun Rerknimitr, Roongruedee Chaiteerakij
Format: Article
Language:English
Published: Nature Portfolio 2022-03-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-022-08678-z
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author Thanikan Sukaram
Rossarin Tansawat
Terapap Apiparakoon
Thodsawit Tiyarattanachai
Sanparith Marukatat
Rungsun Rerknimitr
Roongruedee Chaiteerakij
author_facet Thanikan Sukaram
Rossarin Tansawat
Terapap Apiparakoon
Thodsawit Tiyarattanachai
Sanparith Marukatat
Rungsun Rerknimitr
Roongruedee Chaiteerakij
author_sort Thanikan Sukaram
collection DOAJ
description Abstract Volatile organic compounds (VOCs) profile for diagnosis and monitoring therapeutic response of hepatocellular carcinoma (HCC) has not been well studied. We determined VOCs profile in exhaled breath of 97 HCC patients and 111 controls using gas chromatography–mass spectrometry and Support Vector Machine algorithm. The combination of acetone, 1,4-pentadiene, methylene chloride, benzene, phenol and allyl methyl sulfide provided the highest accuracy of 79.6%, with 76.5% sensitivity and 82.7% specificity in the training set; and 55.4% accuracy, 44.0% sensitivity, and 75.0% specificity in the test set. This combination was correlated with the HCC stages demonstrating by the increased distance from the classification boundary when the stage advanced. For early HCC detection, d-limonene provided a 62.8% sensitivity, 51.8% specificity and 54.9% accuracy. The levels of acetone, butane and dimethyl sulfide were significantly altered after treatment. Patients with complete response had a greater decreased acetone level than those with remaining tumor post-treatment (73.38 ± 56.76 vs. 17.11 ± 58.86 (× 106 AU, p = 0.006). Using a cutoff of 35.9 × 106 AU, the reduction in acetone level predicted treatment response with 77.3% sensitivity, 83.3% specificity, 79.4%, accuracy, and AUC of 0.784. This study demonstrates the feasibility of exhaled VOCs as a non-invasive tool for diagnosis, monitoring of HCC progression and treatment response.
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spelling doaj.art-4d781fe5eb4b47c28c9f45b27a1060ff2022-12-22T03:09:12ZengNature PortfolioScientific Reports2045-23222022-03-011211910.1038/s41598-022-08678-zExhaled volatile organic compounds for diagnosis of hepatocellular carcinomaThanikan Sukaram0Rossarin Tansawat1Terapap Apiparakoon2Thodsawit Tiyarattanachai3Sanparith Marukatat4Rungsun Rerknimitr5Roongruedee Chaiteerakij6Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, and King Chulalongkorn Memorial Hospital, Thai Red Cross SocietyDepartment of Food and Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Chulalongkorn UniversityDepartment of Computer Engineering, Faculty of Engineering, Chulalongkorn UniversityFaculty of Medicine, Chulalongkorn UniversityImage Processing and Understanding Team, Artificial Intelligence Research Group, National Electronics and Computer Technology Center (NECTEC)Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, and King Chulalongkorn Memorial Hospital, Thai Red Cross SocietyDivision of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, and King Chulalongkorn Memorial Hospital, Thai Red Cross SocietyAbstract Volatile organic compounds (VOCs) profile for diagnosis and monitoring therapeutic response of hepatocellular carcinoma (HCC) has not been well studied. We determined VOCs profile in exhaled breath of 97 HCC patients and 111 controls using gas chromatography–mass spectrometry and Support Vector Machine algorithm. The combination of acetone, 1,4-pentadiene, methylene chloride, benzene, phenol and allyl methyl sulfide provided the highest accuracy of 79.6%, with 76.5% sensitivity and 82.7% specificity in the training set; and 55.4% accuracy, 44.0% sensitivity, and 75.0% specificity in the test set. This combination was correlated with the HCC stages demonstrating by the increased distance from the classification boundary when the stage advanced. For early HCC detection, d-limonene provided a 62.8% sensitivity, 51.8% specificity and 54.9% accuracy. The levels of acetone, butane and dimethyl sulfide were significantly altered after treatment. Patients with complete response had a greater decreased acetone level than those with remaining tumor post-treatment (73.38 ± 56.76 vs. 17.11 ± 58.86 (× 106 AU, p = 0.006). Using a cutoff of 35.9 × 106 AU, the reduction in acetone level predicted treatment response with 77.3% sensitivity, 83.3% specificity, 79.4%, accuracy, and AUC of 0.784. This study demonstrates the feasibility of exhaled VOCs as a non-invasive tool for diagnosis, monitoring of HCC progression and treatment response.https://doi.org/10.1038/s41598-022-08678-z
spellingShingle Thanikan Sukaram
Rossarin Tansawat
Terapap Apiparakoon
Thodsawit Tiyarattanachai
Sanparith Marukatat
Rungsun Rerknimitr
Roongruedee Chaiteerakij
Exhaled volatile organic compounds for diagnosis of hepatocellular carcinoma
Scientific Reports
title Exhaled volatile organic compounds for diagnosis of hepatocellular carcinoma
title_full Exhaled volatile organic compounds for diagnosis of hepatocellular carcinoma
title_fullStr Exhaled volatile organic compounds for diagnosis of hepatocellular carcinoma
title_full_unstemmed Exhaled volatile organic compounds for diagnosis of hepatocellular carcinoma
title_short Exhaled volatile organic compounds for diagnosis of hepatocellular carcinoma
title_sort exhaled volatile organic compounds for diagnosis of hepatocellular carcinoma
url https://doi.org/10.1038/s41598-022-08678-z
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