Headspace Volatile Organic Compound Profiling of Pleural Mesothelioma and Lung Cancer Cell Lines as Translational Bridge for Breath Research

Our plain-English summary of Headspace Volatile Organic Compound Profiling of Pleural Mesothelioma and Lung Cancer Cell Lines as Translational Bridge for Breath Research, by E. Janssens, Z. Mol, L. Vandermeersch, et al (Frontiers in Oncology, 2022).

The study

• Authors: E. Janssens, Z. Mol, L. Vandermeersch, S. Lagniau, K.Y. Vermaelen, J.P. van Meerbeeck, C. Walgraeve, E. Marcq, K. Lamote
• Journal: Frontiers in Oncology
• Published: 2022;12:851785
• Cited by: 13 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Introduction: Malignant pleural mesothelioma (MPM) is a lethal cancer for which early-stage diagnosis remains a major challenge. Volatile organic compounds (VOCs) in breath proved to be potential biomarkers for MPM diagnosis, but translational studies are needed to elucidate which VOCs originate from the tumor itself and thus are specifically related to MPM cell metabolism.

Methods: An in vitro model was set-up to characterize the headspace VOC profiles of six MPM and two lung cancer cell lines using thermal desorption-gas chromatography-mass spectrometry. A comparative analysis was carried out to identify VOCs that could discriminate between MPM and lung cancer, as well as between the histological subtypes within MPM (epithelioid, sarcomatoid and biphasic).

Results: VOC profiles were identified capable of distinguishing MPM (subtypes) and lung cancer cells with high accuracy. Alkanes, aldehydes, ketones and alcohols represented many of the discriminating VOCs. Discrepancies with clinical findings were observed, supporting the need for studies examining breath and tumor cells of the same patients and studying metabolization and kinetics of in vitro discovered VOCs in a clinical setting.

Conclusion: While the relationship between in vitro and in vivo VOCs is yet to be established, both could complement each other in generating a clinically useful breath model for MPM.

Copyright © 2022 Janssens, Mol, Vandermeersch, Lagniau, Vermaelen, van Meerbeeck, Walgraeve, Marcq and Lamote.

In plain English

This laboratory study measured volatile organic compounds (VOCs), chemicals breath tests target, released by cancer cells. The authors sampled air above six malignant pleural mesothelioma (MPM) cell lines (two each epithelioid, sarcomatoid, biphasic) and two non-small cell lung cancer lines after 48 hours. Of 277 peaks, 77 were identified; each line had its own profile. With 28 mesothelioma and 5 lung cancer culture samples, a statistical model reached 97.0% accuracy (95% confidence interval 86.0 to 99.9), 80.0% sensitivity (33.5 to 99.0) and 100% specificity (89.9 to 100). Against lung cancer, accuracy was 100% for epithelioid (10 versus 5 samples; interval 81.9 to 100) and biphasic (8 versus 5; 79.4 to 100), but 66.7% for sarcomatoid (10 versus 5; 40.1 to 86.6). Between subtypes (10 epithelioid, 10 sarcomatoid, 8 biphasic samples), sensitivity, specificity and accuracy ranged from 90 to 100% (lowest accuracy interval bound 70.8%). Overlap with compounds in patients' breath was limited; stated limits included 2D culture and possible outside compound sources. The authors concluded cell and breath findings could complement each other toward a clinically useful MPM breath model.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: In vitro laboratory study: chemical analysis (thermal desorption-gas chromatography-mass spectrometry) of the air above cultured cancer cell lines, with statistical classification models (lasso regression, leave-one-out cross-validation)
• Who was studied: Six human malignant pleural mesothelioma cell lines: two sarcomatoid (NCI-H2731, H-MESO-1), two epithelioid (NCI-H2795, NCI-H2818) and two biphasic (NKI04, MSTO-211H). Also two non-small cell lung cancer cell lines (NCI-H2228, NCI-H1975), with flasks of blank culture medium as controls. In total 28 mesothelioma and 5 lung cancer culture samples were used in the main comparison. No human participants.
• Exposure: No asbestos or other exposure was studied. The study measured volatile organic compounds released by cells into the flask air after 48 hours of incubation.
• Main results:
  • 277 VOC peaks were detected across the samples, of which 77 could be identified.
  • Each cell line produced a distinct VOC profile. The two cell lines of the same mesothelioma subtype, and the two lung cancer cell lines, did not cluster together.
  • Number of culture samples in each comparison: mesothelioma versus lung cancer 28 versus 5; epithelioid versus lung cancer 10 versus 5; sarcomatoid versus lung cancer 10 versus 5; biphasic versus lung cancer 8 versus 5; epithelioid versus sarcomatoid 10 versus 10; sarcomatoid versus biphasic 10 versus 8; biphasic versus epithelioid 8 versus 10.
  • Mesothelioma cells versus lung cancer cells (28 versus 5 samples): 97.0% accuracy (95% CI 86.0 to 99.9), 80.0% sensitivity (33.5 to 99.0), 100% specificity (89.9 to 100), area under the curve 0.964 (0.871 to 1.000).
  • Twenty-four VOCs were important in separating mesothelioma from lung cancer cells. Only two of them, propylbenzene and trichloromethane, could be identified.
  • Epithelioid (10 versus 5 samples) and biphasic (8 versus 5 samples) mesothelioma cells were each separated from lung cancer cells with 100% sensitivity, specificity and accuracy, and an area under the curve of 1.000. The 95% confidence intervals for accuracy were 81.9 to 100 (epithelioid) and 79.4 to 100 (biphasic).
  • Sarcomatoid mesothelioma cells versus lung cancer cells (10 versus 5 samples): 70.0% sensitivity, 60.0% specificity, 66.7% accuracy (95% CI 40.1 to 86.6), area under the curve 0.740 (0.460 to 0.960).
  • The three mesothelioma subtypes (10 epithelioid, 10 sarcomatoid and 8 biphasic samples) were distinguished from one another with sensitivity, specificity and accuracy values ranging from 90 to 100%.
  • Accuracy with 95% confidence intervals, in table order: mesothelioma versus lung cancer 97.0 (86.0 to 99.9); epithelioid versus lung cancer 100 (81.9 to 100); sarcomatoid versus lung cancer 66.7 (40.1 to 86.6); biphasic versus lung cancer 100 (79.4 to 100); epithelioid versus sarcomatoid 90.0 (70.8 to 98.3); sarcomatoid versus biphasic 94.4 (75.6 to 99.7); biphasic versus epithelioid 100 (84.7 to 100).
  • The VOCs found in these cell experiments showed only limited overlap with VOCs proposed as breath biomarkers in clinical studies of mesothelioma.
• The authors' conclusion: The authors concluded that they had identified MPM-specific VOC profiles that distinguished MPM subtypes and lung cancer cells with high accuracy. They noted discrepancies with breath profiles reported in patients, and said cell and breath findings could complement each other in building a clinically useful breath model for MPM.
• Limitations the authors state:
  • Cells were grown in standard 2D culture, which does not reproduce the 3D structure and low-oxygen environment of tumors in the body.
  • Mesothelioma cells were not compared with normal (non-malignant) mesothelial cells; lung cancer cells were used as the comparison group instead.
  • Despite background correction for culture media, materials and sampling environment, some measured VOCs may not have come from the cells themselves.
  • Trichloromethane, one of the two identified compounds separating mesothelioma from lung cancer cells, could be a solvent contaminant.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Lung Cancer, Biomarker, Histological Subtype, Epithelioid, Sarcomatoid, Biphasic Mesothelioma.

Related studies

• Asbestos mineral fibre exposure significantly affects volatile organic compound profiles of mesothelial cell lines in vitro — S. Bonsall, T. Issitt, et al. (2026)
• Breath Analysis for Early Detection of Malignant Pleural Mesothelioma: Volatile Organic Compounds (VOCs) Determination and Possible Biochemical Pathways — A. Di Gilio, A. Catino, et al. (2020)
• Breath Analysis: A Systematic Review of Volatile Organic Compounds (VOCs) in Diagnostic and Therapeutic Management of Pleural Mesothelioma — A. Catino, G. de Gennaro, et al. (2019)
• Volatile organic compounds in exhaled human breath for the diagnosis of malignant pleural mesothelioma: a meta-analysis — T. Zhao, X. Hu, et al. (2025)
• Assessing truck driver exposure at the World Trade Center disaster site: personal and area monitoring for particulate matter and volatile organic compounds during October 2001 and April 2002 — A.S. Geyh, S. Chillrud, et al. (2005)
• Volatile organic compound analysis of malignant pleural mesothelioma chorioallantoic membrane xenografts — L.D. Little, S.E. Barnett, et al. (2024)

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