Abstract
Introduction
Thyroid cancer incidence rate has increased substantially worldwide in recent years. Fine needle aspiration biopsy (FNAB) is currently the golden standard of thyroid cancer diagnosis, which however, is invasive and costly. In contrast, breath analysis is a non-invasive, safe and simple sampling method combined with a promising metabolomics approach, which is suitable for early cancer diagnosis in high volume population.
Objectives
This study aims to achieve a more comprehensive and definitive exhaled breath metabolism profile in papillary thyroid cancer patients (PTCs).
Methods
We studied both end-tidal and mixed expiratory breath, solid-phase microextraction gas chromatography coupled with high resolution mass spectrometry (SPME-GC-HRMS) was used to analyze the breath samples. Multivariate combined univariate analysis was applied to identify potential breath biomarkers.
Results
The biomarkers identified in end-tidal and mixed expiratory breath mainly included alkanes, olefins, enols, enones, esters, aromatic compounds, and fluorine and chlorine containing organic compounds. The area under the curve (AUC) values of combined biomarkers were 0.974 (sensitivity: 96.1%, specificity: 90.2%) and 0.909 (sensitivity: 98.0%, specificity: 74.5%), respectively, for the end-tidal and mixed expiratory breath, indicating of reliability of the sampling and analysis method
Conclusion
This work not only successfully established a standard metabolomic approach for early diagnosis of PTC, but also revealed the necessity of using both the two breath types for comprehensive analysis of the biomarkers.
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Data availability
All data and materials are stored in the Research Center of Analytical Instrumentation, Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of Ministry of Education, College of Chemistry & Materials Science, Northwest University, **’an, Shaanxi, 710069, China. The data are confidential due to ethical concerns.
Abbreviations
- FNAB:
-
Fine needle aspiration biopsy
- PTCs:
-
Papillary thyroid carcinoma patients
- HCs:
-
Healthy controls
- SPME-GC-HRMS:
-
Solid-phase microextraction gas chromatography-high resolution mass spectrometry
- ROC:
-
Receiver operator characteristic curve
- AUC:
-
Area under the curve
- VOCs:
-
Volatile organic compounds
- PCA:
-
Principal component analysis
- OPLS-DA:
-
Orthogonal partial least squares discriminant analysis
- PDMS:
-
Polydimethylsiloxane
- CAR/PDMS:
-
Carboxen/polydimethylsiloxane
- PDMS/DVB:
-
Polydimethylsiloxane/divinylbenzene
- DVB/CAR/PDMS:
-
Divinylbenzene/carboxen/polydimethylsiloxane
- TICs:
-
Total ion chromatograms
- NIST:
-
National institute of standards and technology
- RT:
-
Retention time
- VIP:
-
Variable importance for the projection
- CYP450:
-
Cytochrome p450 enzyme
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Acknowledgements
This study has been registered in the Chinese Clinical Trials Registry (http://www.chictr.org.cn) with registration number ChiCTR2200067225 on December 29, 2022. The authors are grateful to the patients and healthy volunteers who agreed to participate in this study.
Funding
This study was funded by the Startup Funding of Northwest University for setting up the Research Center of Analytical Instrumentation, National Key Research and Development Project (2018YFC1800903), and Key Research and Development Program of Shaanxi Province of China (2019ZDLSF01-03).
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Lan Li: Conceptualization, Data curation, Methodology, Software, Writing—original draft. **nxin Wen: Conceptualization, Investigation, Writing—original draft. **an Li: Writing—review & editing. Yaqi Yan: Writing—review & editing. Jiayu Wang: Writing—review & editing. Xuyang Zhao: Writing—review & editing. Yonghui Tian: Writing—review & editing. Rui Ling: Conceptualization, Project administration. Yixiang Duan: Conceptualization, Project administration, Funding acquisition. All authors read and approved the manuscript.
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The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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Collection of human exhaled breath for research in this study was approved by the medical ethics committee of the Northwest University (**'an, China) (No. 20221212001) and ****g Hospital, the First Affiliated Hospital of the Air Force Military Medical University (**'an, China). This study was carried out in accordance with the ethical guidelines of the Declaration of Helsinki.
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Li, L., Wen, X., Li, X. et al. Identifying potential breath biomarkers for early diagnosis of papillary thyroid cancer based on solid-phase microextraction gas chromatography-high resolution mass spectrometry with metabolomics. Metabolomics 20, 59 (2024). https://doi.org/10.1007/s11306-024-02119-w
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DOI: https://doi.org/10.1007/s11306-024-02119-w