VOCs from Exhaled Breath for the Diagnosis of Hepatocellular Carcinoma

Background: Volatile organic compound (VOC) profiles as biomarkers for hepatocellular carcinoma (HCC) are understudied. We aimed to identify VOCs from the exhaled breath for HCC diagnosis and compare the performance of VOCs to alpha-fetoprotein (AFP). The performance of VOCs for predicting treatment...

Full description

Bibliographic Details
Main Authors: Thanikan Sukaram, Terapap Apiparakoon, Thodsawit Tiyarattanachai, Darlene Ariyaskul, Kittipat Kulkraisri, Sanparith Marukatat, Rungsun Rerknimitr, Roongruedee Chaiteerakij
Format: Article
Language:English
Published: MDPI AG 2023-01-01
Series:Diagnostics
Subjects:
Online Access:https://www.mdpi.com/2075-4418/13/2/257
_version_ 1797443817236856832
author Thanikan Sukaram
Terapap Apiparakoon
Thodsawit Tiyarattanachai
Darlene Ariyaskul
Kittipat Kulkraisri
Sanparith Marukatat
Rungsun Rerknimitr
Roongruedee Chaiteerakij
author_facet Thanikan Sukaram
Terapap Apiparakoon
Thodsawit Tiyarattanachai
Darlene Ariyaskul
Kittipat Kulkraisri
Sanparith Marukatat
Rungsun Rerknimitr
Roongruedee Chaiteerakij
author_sort Thanikan Sukaram
collection DOAJ
description Background: Volatile organic compound (VOC) profiles as biomarkers for hepatocellular carcinoma (HCC) are understudied. We aimed to identify VOCs from the exhaled breath for HCC diagnosis and compare the performance of VOCs to alpha-fetoprotein (AFP). The performance of VOCs for predicting treatment response and the association between VOCs level and survival of HCC patients were also determined. Methods: VOCs from 124 HCC patients and 219 controls were identified using the XGBoost algorithm. ROC analysis was used to determine VOCs performance in differentiating HCC patients from controls and in discriminating treatment responders from non-responders. The association between VOCs and the survival of HCC patients was analyzed using Cox proportional hazard analysis. Results: The combination of 9 VOCs yielded 70.0% sensitivity, 88.6% specificity, and 75.0% accuracy for HCC diagnosis. When differentiating early HCC from cirrhotic patients, acetone dimer had a significantly higher AUC than AFP, i.e., 0.775 vs. 0.714, respectively, <i>p</i> = 0.001. Acetone dimer classified HCC patients into treatment responders and non-responders, with 95.7% sensitivity, 73.3% specificity, and 86.8% accuracy. Isopropyl alcohol was independently associated with the survival of HCC patients, with an adjusted hazard ratio of 7.23 (95%CI: 1.36–38.54), <i>p</i> = 0.020. Conclusions: Analysis of VOCs is a feasible noninvasive test for diagnosing and monitoring HCC treatment response.
first_indexed 2024-03-09T13:02:30Z
format Article
id doaj.art-2e35811f2267438aaade82b42bf9ae1d
institution Directory Open Access Journal
issn 2075-4418
language English
last_indexed 2024-03-09T13:02:30Z
publishDate 2023-01-01
publisher MDPI AG
record_format Article
series Diagnostics
spelling doaj.art-2e35811f2267438aaade82b42bf9ae1d2023-11-30T21:52:12ZengMDPI AGDiagnostics2075-44182023-01-0113225710.3390/diagnostics13020257VOCs from Exhaled Breath for the Diagnosis of Hepatocellular CarcinomaThanikan Sukaram0Terapap Apiparakoon1Thodsawit Tiyarattanachai2Darlene Ariyaskul3Kittipat Kulkraisri4Sanparith Marukatat5Rungsun Rerknimitr6Roongruedee Chaiteerakij7Program in Medical Sciences, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, ThailandDepartment of Computer Engineering, Faculty of Engineering, Chulalongkorn University, Bangkok 10330, ThailandFaculty of Medicine, Chulalongkorn University, Bangkok 10330, ThailandFaculty of Medicine, Chulalongkorn University, Bangkok 10330, ThailandFaculty of Medicine, Chulalongkorn University, Bangkok 10330, ThailandImage Processing and Understanding Team, Artificial Intelligence Research Group, National Electronics and Computer Technology Center (NECTEC), Pathum Thani 12120, ThailandDivision of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, ThailandDivision of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, ThailandBackground: Volatile organic compound (VOC) profiles as biomarkers for hepatocellular carcinoma (HCC) are understudied. We aimed to identify VOCs from the exhaled breath for HCC diagnosis and compare the performance of VOCs to alpha-fetoprotein (AFP). The performance of VOCs for predicting treatment response and the association between VOCs level and survival of HCC patients were also determined. Methods: VOCs from 124 HCC patients and 219 controls were identified using the XGBoost algorithm. ROC analysis was used to determine VOCs performance in differentiating HCC patients from controls and in discriminating treatment responders from non-responders. The association between VOCs and the survival of HCC patients was analyzed using Cox proportional hazard analysis. Results: The combination of 9 VOCs yielded 70.0% sensitivity, 88.6% specificity, and 75.0% accuracy for HCC diagnosis. When differentiating early HCC from cirrhotic patients, acetone dimer had a significantly higher AUC than AFP, i.e., 0.775 vs. 0.714, respectively, <i>p</i> = 0.001. Acetone dimer classified HCC patients into treatment responders and non-responders, with 95.7% sensitivity, 73.3% specificity, and 86.8% accuracy. Isopropyl alcohol was independently associated with the survival of HCC patients, with an adjusted hazard ratio of 7.23 (95%CI: 1.36–38.54), <i>p</i> = 0.020. Conclusions: Analysis of VOCs is a feasible noninvasive test for diagnosing and monitoring HCC treatment response.https://www.mdpi.com/2075-4418/13/2/257volatile organic compounds (VOCs)biomarkerscancer diagnosisbreath samplesmachine learningField Asymmetric Ion Mobility Spectrometry (FAIMS)
spellingShingle Thanikan Sukaram
Terapap Apiparakoon
Thodsawit Tiyarattanachai
Darlene Ariyaskul
Kittipat Kulkraisri
Sanparith Marukatat
Rungsun Rerknimitr
Roongruedee Chaiteerakij
VOCs from Exhaled Breath for the Diagnosis of Hepatocellular Carcinoma
Diagnostics
volatile organic compounds (VOCs)
biomarkers
cancer diagnosis
breath samples
machine learning
Field Asymmetric Ion Mobility Spectrometry (FAIMS)
title VOCs from Exhaled Breath for the Diagnosis of Hepatocellular Carcinoma
title_full VOCs from Exhaled Breath for the Diagnosis of Hepatocellular Carcinoma
title_fullStr VOCs from Exhaled Breath for the Diagnosis of Hepatocellular Carcinoma
title_full_unstemmed VOCs from Exhaled Breath for the Diagnosis of Hepatocellular Carcinoma
title_short VOCs from Exhaled Breath for the Diagnosis of Hepatocellular Carcinoma
title_sort vocs from exhaled breath for the diagnosis of hepatocellular carcinoma
topic volatile organic compounds (VOCs)
biomarkers
cancer diagnosis
breath samples
machine learning
Field Asymmetric Ion Mobility Spectrometry (FAIMS)
url https://www.mdpi.com/2075-4418/13/2/257
work_keys_str_mv AT thanikansukaram vocsfromexhaledbreathforthediagnosisofhepatocellularcarcinoma
AT terapapapiparakoon vocsfromexhaledbreathforthediagnosisofhepatocellularcarcinoma
AT thodsawittiyarattanachai vocsfromexhaledbreathforthediagnosisofhepatocellularcarcinoma
AT darleneariyaskul vocsfromexhaledbreathforthediagnosisofhepatocellularcarcinoma
AT kittipatkulkraisri vocsfromexhaledbreathforthediagnosisofhepatocellularcarcinoma
AT sanparithmarukatat vocsfromexhaledbreathforthediagnosisofhepatocellularcarcinoma
AT rungsunrerknimitr vocsfromexhaledbreathforthediagnosisofhepatocellularcarcinoma
AT roongruedeechaiteerakij vocsfromexhaledbreathforthediagnosisofhepatocellularcarcinoma