Volatile organic compound analysis of malignant pleural mesothelioma chorioallantoic membrane xenografts

Our plain-English summary of Volatile organic compound analysis of malignant pleural mesothelioma chorioallantoic membrane xenografts, by L.D. Little, S.E. Barnett, T. Issitt, et al (Journal of Breath Research, 2024).

The study

• Authors: L.D. Little, S.E. Barnett, T. Issitt, S. Bonsall, V.A. Carolan, E. Allen, L.M. Cole, N.A. Cross, J.M. Coulson, S.L. Haywood-Small
• Journal: Journal of Breath Research
• Published: 2024;18(4)
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is an aggressive cancer associated with asbestos exposure. MPM is often diagnosed late, at a point where limited treatment options are available, but early intervention could improve the chances of successful treatment for MPM patients. Biomarkers to detect MPM in at-risk individuals are needed to implement early diagnosis technologies. Volatile organic compounds (VOCs) have previously shown diagnostic potential as biomarkers when analysed in MPM patient breath. In this study, chorioallantoic membrane (CAM) xenografts of MPM cell lines were used as models of MPM tumour development for VOC biomarker discovery with the aim of generating targets for investigation in breath, biopsies or other complex matrices. VOC headspace analysis of biphasic or epithelioid MPM CAM xenografts was performed using solid-phase microextraction and gas chromatography-mass spectrometry. We successfully demonstrated the capture, analysis and separation of VOC signatures from CAM xenografts and controls. A panel of VOCs was identified that showed discrimination between MPM xenografts generated from biphasic and epithelioid cells and CAM controls. This is the first application of the CAM xenograft model for the discovery of VOC biomarkers associated with MPM histological subtypes. These findings support the potential utility of non-invasive VOC profiling from breath or headspace analysis of tissues for detection and monitoring of MPM.

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In plain English

This was a laboratory study, not a study of people or of asbestos exposure. The authors grew tumours from three mesothelioma cell lines on the chorioallantoic membrane (CAM) of fertilised hens' eggs. One line, 7T, came from biphasic disease; the other two, 8T and 12T, came from epithelioid disease. They compared volatile organic compounds (VOCs) given off by the excised tumours with those from untreated and mock-treated egg membranes. Of 1489 detected features, 94 differed significantly from background. Nineteen compounds, which the authors identified only tentatively, drove the separation between groups. A model using all nineteen distinguished tumours from controls with an area under the curve of 0.99 (0.919 with 2 compounds). Epithelioid tumours were separated from biphasic tumours with 0.951 using 2 compounds and 1 using more than five. The authors concluded that the model shows potential for finding VOC biomarkers of mesothelioma. They called the subtype results preliminary and based on a limited set of cells, and said further work is needed to understand where the VOCs come from.

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: Laboratory experiment using chick embryo chorioallantoic membrane (CAM) xenografts of human mesothelioma cell lines, with headspace VOC analysis by solid-phase microextraction and gas chromatography-mass spectrometry
• Who was studied: Tumours grown on fertilised hens' eggs from three malignant pleural mesothelioma cell lines obtained from Mesobank: MESO-7T (biphasic), MESO-8T and MESO-12T (epithelioid). Harvested tumours were 12T n = 7, 8T n = 9 and 7T n = 5. These were compared with untreated control and mock-implanted CAM samples.
• Exposure: No asbestos exposure was studied. The comparison was between mesothelioma cell-line tumours implanted on the CAM and CAM without tumour cells; VOCs were measured from the excised tissue.
• Main results:
  • 94 features out of 1489 were significantly different from the background (preservative-only) samples and were used for further analysis
  • In unsupervised analysis, the biphasic 7T xenografts could not be separated from control or mock samples
  • Untreated and mock-implanted control membranes could not be separated from each other
  • Nineteen compounds were the main drivers of group separation and were given tentative identification
  • Pentanoic acid was raised in all three xenograft types compared with controls
  • Combined tumours (7T, 8T, 12T) versus combined controls: area under the curve 0.919 using 2 compounds and 0.99 using all nineteen
  • Epithelioid (8T and 12T) versus biphasic (7T) xenografts: 0.951 using 2 compounds and 1 using more than five
• The authors' conclusion: The authors concluded that the CAM xenograft model shows potential for discovering VOC biomarkers in malignant pleural mesothelioma and in cancer more generally
• Limitations the authors state:
  • The subtype findings rest on a limited set of cell lines (one biphasic, two epithelioid); the authors called these data preliminary
  • Control membranes were not weighed, so tumour weight could not be compared directly with CAM weight
  • Further development is needed to understand where the VOCs come from

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Asbestos Exposure, Biomarker, Discovery, Biphasic Mesothelioma, Epithelioid, Histological Subtype.

Related studies

• 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)
• 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)
• 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)
• Chemical characterization of exhaled breath to differentiate between patients with malignant plueral mesothelioma from subjects with similar professional asbestos exposure — G. de Gennaro, S. Dragonieri, et al. (2010)
• Exhaled Breath Analysis in Diagnosis of Malignant Pleural Mesothelioma: Systematic Review — Z.N. Töreyin, M. Ghosh, et al. (2020)
• Electronic Nose Technology in Respiratory Diseases — S. Dragonieri, G. Pennazza, et al. (2017)

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