Identification and diagnostic value of characteristic volatile organic compounds in exhaled breath of patients with early stage lung cancer_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

PENG Xiaoqin ¹ , LIU Mingxin ^2,3 , DAI Wei ² , XIE Shaohua ² , XIANG Run ² , ZHANG Fengyi ⁴ ,  LI Qiang ²

1. Department of Oncology, Nanchong Central Hospital, The Second Clinical Medical College of North Sichuan Medical College, Nanchong, 637000, Sichuan, P.R.China;
2. Department of Thoracic Surgery, Sichuan Cancer Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610041, P.R.China;
3. School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610054, P.R.China;
4. Department of Thoracic Surgery, Nanchong Central Hospital, The Second Clinical Medical College of North Sichuan Medical College, Nanchong, 637000, Sichuan, P.R.China;

Corresponding author：

LI Qiang, Email: liqiang@sichuancancer.org

Keywords：

Lung cancer; early diagnosis; exhaled breath; volatile organic compounds; diagnostic model

DOI：

10.7507/1007-4848.202003019

Video：

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Objective To investigate the characteristic volatile organic compounds (VOCs) in exhaled breath and their diagnostic value in patients with early stage lung cancer.Methods Solid-phase micro-extraction combined with gas chromatography mass spectrometry was used to analyze exhaled breath VOCs of 117 patients with early stage lung cancer (54 males and 63 females, with an average age of 61.9±6.8 years) and 130 healthy subjects (79 males and 51 females, with an average age of 63.3±6.6 years. The characteristic VOCs of early stage lung cancer were identified, and a diagnostic model was established.Results Ten characteristic VOCs of early stage lung cancer were identified, including acetic acid, n-butanol, dimethylsilanol, toluene, 2,3,4-trimethylheptane, 3,4-dimethylbenzoic acid, 5-methyl-3-hexene-2-ketone, n-hexanol, methyl 2-oxoglutarate and 4-methoxyphenol. Gender and the 10 characteristic VOCs were included in the diagnostic model, with a sensitivity of 83.8% and a specificity of 96.2%.Conclusion Analysis of exhaled breath VOCs is expected to be one of the potential methods used for early stage lung cancer diagnosis.

Citation： PENG Xiaoqin, LIU Mingxin, DAI Wei, XIE Shaohua, XIANG Run, ZHANG Fengyi, LI Qiang. Identification and diagnostic value of characteristic volatile organic compounds in exhaled breath of patients with early stage lung cancer. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2020, 27(12): 1429-1435. doi: 10.7507/1007-4848.202003019 Copy

1.	Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018, 68(6): 394-424.
2.	Allemani C, Matsuda T, Di Carlo V, et al. Global surveillance of trends in cancer survival 2000-14 (CONCORD-3): analysis of individual records for 37513025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries. Lancet, 2018, 391(10125): 1023-1075.
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5.	甄丽芳, 凌敏. 肺癌早期诊断现状与未来展望. 临床肺科杂志, 2017, 22(3): 549-553.
6.	Scarlata S, Pennazza G, Santonico M, et al. Exhaled breath analysis by electronic nose in respiratory diseases. Expert Rev Mol Diagn, 2015, 15(7): 933-956.
7.	Queralto N, Berliner AN, Goldsmith B, et al. Detecting cancer by breath volatile organic compound analysis: a review of array-based sensors. J Breath Res, 2014, 8(2): 027112.
8.	Kabir KMM, Donald WA. Cancer breath testing: a patent review. Expert Opin Ther Pat, 2018, 28(3): 227-239.
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10.	Kamboures MA, Blake DR, Cooper DM, et al. Breath sulfides and pulmonary function in cystic fibrosis. Proc Natl Acad Sci U S A, 2005, 102(44): 15762-15767.
11.	Hua Q, Zhu Y, Liu H. Detection of volatile organic compounds in exhaled breath to screen lung cancer: a systematic review. Future Oncol, 2018, 14(16): 1647-1662.
12.	Phillips M, Altorki N, Austin JH, et al. Prediction of lung cancer using volatile biomarkers in breath. Cancer Biomark, 2007, 3(2): 95-109.
13.	胡燕婕. 肺癌呼气特征性 VOCs 的筛选及诊断价值研究. 浙江大学医学院, 2010.
14.	Boshier PR, Priest OH, Hanna GB, et al. Influence of respiratory variables on the on-line detection of exhaled trace gases by PTR-MS. Thorax, 2011, 66(10): 919-920.
15.	Finamore P, Scarlata, S, Incalzi RA. Breath analysis in respiratory diseases: state-of-the-art and future perspectives. Expert Rev Mol Diagn, 2019, 19(1): 47-61.
16.	王怡珊. 肺癌呼出气体标志物确定及电子鼻临床诊断方法研究. 浙江大学, 2012.
17.	Miekisch W, Herbig J, Schubert JK. Data interpretation in breath biomarker research: pitfalls and directions. J Breath Res, 2012, 6(3): 036007.
18.	Bajtarevic A, Ager C, Pienz M, et al. Noninvasive detection of lung cancer by analysis of exhaled breath. BMC Cancer, 2009, 9: 348.
19.	Remmer H, Hintze T, Frańk H, et al. Cytochrome P-450 oxidation of alkanes originating as scission products during lipid peroxidation. Xenobiotica, 1984, 14(1): 207-219.
20.	Mazzone PJ, Hammel J, Dweik R, et al. Diagnosis of lung cancer by the analysis of exhaled breath with a colorimetric sensor array. Thorax, 2007, 62(7): 565-568.
21.	Peng G, Hakim M, Broza YY, et al. Detection of lung, breast, colorectal, and prostate cancers from exhaled breath using a single array of nanosensors. Br J Cancer, 2010, 103(4): 542-551.
22.	Dragonieri S, Schot R, Mertens BJ, et al. An electronic nose in the discrimination of patients with asthma and controls. J Allergy Clin Immunol, 2007, 120(4): 856-862.
23.	Phillips M, Cataneo RN, Greenberg J, et al. Effect of age on the breath methylated alkane contour, a display of apparent new markers of oxidative stress. J Lab Clin Med, 2000, 136(3): 243-249.
24.	Horváth I, Lázár Z, Gyulai N, et al. Exhaled biomarkers in lung cancer. Eur Respir J, 2009, 34(1): 261-275.
25.	Capone S, Tufariello M, Forleo A, et al. Chromatographic analysis of VOC patterns in exhaled breath from smokers and nonsmokers. Biomed Chromatogr, 2018, 32(4).
26.	Alonso M, Castellanos M, Sanchez JM. Evaluation of potential breath biomarkers for active smoking: assessment of smoking habits. Anal Bioanal Chem, 2010, 396(8): 2987-2995.
27.	Field JK, Smith RA, Aberle DR, et al. International Association for the Study of Lung Cancer Computed Tomography Screening Workshop 2011 report. J Thorac Oncol, 2012, 7(1): 10-19.
28.	Wagnetz U, Menezes RJ, Boerner S, et al. CT screening for lung cancer: implication of lung biopsy recommendations. AJR Am J Roentgenol, 2012, 198(2): 351-358.
29.	Di Natale C, Macagnano A, Martinelli E, et al. Lung cancer identification by the analysis of breath by means of an array of non-selective gas sensors. Biosens Bioelectron, 2003, 18(10): 1209-1218.
30.	Phillips M, Altorki N, Austin JH, et al. Detection of lung cancer using weighted digital analysis of breath biomarkers. Clin Chim Acta, 2008, 393(2): 76-84.

1. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018, 68(6): 394-424.
2. Allemani C, Matsuda T, Di Carlo V, et al. Global surveillance of trends in cancer survival 2000-14 (CONCORD-3): analysis of individual records for 37513025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries. Lancet, 2018, 391(10125): 1023-1075.
3. Goldstraw P, Chansky K, Crowley J, et al. The IASLC Lung Cancer Staging Project: Proposals for revision of the TNM stage groupings in the forthcoming (Eighth) Edition of the TNM Classification for Lung Cancer. J Thorac Oncol, 2016, 11(1): 39-51.
4. 周清华, 范亚光, 王颖, 等. 中国肺癌低剂量螺旋 CT 筛查指南 (2018 年版). 中国肺癌杂志, 2018, 21(2): 67-75.
5. 甄丽芳, 凌敏. 肺癌早期诊断现状与未来展望. 临床肺科杂志, 2017, 22(3): 549-553.
6. Scarlata S, Pennazza G, Santonico M, et al. Exhaled breath analysis by electronic nose in respiratory diseases. Expert Rev Mol Diagn, 2015, 15(7): 933-956.
7. Queralto N, Berliner AN, Goldsmith B, et al. Detecting cancer by breath volatile organic compound analysis: a review of array-based sensors. J Breath Res, 2014, 8(2): 027112.
8. Kabir KMM, Donald WA. Cancer breath testing: a patent review. Expert Opin Ther Pat, 2018, 28(3): 227-239.
9. Miekisch W, Schubert JK, Noeldge-Schomburg GF. Diagnostic potential of breath analysis-focus on volatile organic compounds. Clin Chim Acta, 2004, 347(1): 25-39.
10. Kamboures MA, Blake DR, Cooper DM, et al. Breath sulfides and pulmonary function in cystic fibrosis. Proc Natl Acad Sci U S A, 2005, 102(44): 15762-15767.
11. Hua Q, Zhu Y, Liu H. Detection of volatile organic compounds in exhaled breath to screen lung cancer: a systematic review. Future Oncol, 2018, 14(16): 1647-1662.
12. Phillips M, Altorki N, Austin JH, et al. Prediction of lung cancer using volatile biomarkers in breath. Cancer Biomark, 2007, 3(2): 95-109.
13. 胡燕婕. 肺癌呼气特征性 VOCs 的筛选及诊断价值研究. 浙江大学医学院, 2010.
14. Boshier PR, Priest OH, Hanna GB, et al. Influence of respiratory variables on the on-line detection of exhaled trace gases by PTR-MS. Thorax, 2011, 66(10): 919-920.
15. Finamore P, Scarlata, S, Incalzi RA. Breath analysis in respiratory diseases: state-of-the-art and future perspectives. Expert Rev Mol Diagn, 2019, 19(1): 47-61.
16. 王怡珊. 肺癌呼出气体标志物确定及电子鼻临床诊断方法研究. 浙江大学, 2012.
17. Miekisch W, Herbig J, Schubert JK. Data interpretation in breath biomarker research: pitfalls and directions. J Breath Res, 2012, 6(3): 036007.
18. Bajtarevic A, Ager C, Pienz M, et al. Noninvasive detection of lung cancer by analysis of exhaled breath. BMC Cancer, 2009, 9: 348.
19. Remmer H, Hintze T, Frańk H, et al. Cytochrome P-450 oxidation of alkanes originating as scission products during lipid peroxidation. Xenobiotica, 1984, 14(1): 207-219.
20. Mazzone PJ, Hammel J, Dweik R, et al. Diagnosis of lung cancer by the analysis of exhaled breath with a colorimetric sensor array. Thorax, 2007, 62(7): 565-568.
21. Peng G, Hakim M, Broza YY, et al. Detection of lung, breast, colorectal, and prostate cancers from exhaled breath using a single array of nanosensors. Br J Cancer, 2010, 103(4): 542-551.
22. Dragonieri S, Schot R, Mertens BJ, et al. An electronic nose in the discrimination of patients with asthma and controls. J Allergy Clin Immunol, 2007, 120(4): 856-862.
23. Phillips M, Cataneo RN, Greenberg J, et al. Effect of age on the breath methylated alkane contour, a display of apparent new markers of oxidative stress. J Lab Clin Med, 2000, 136(3): 243-249.
24. Horváth I, Lázár Z, Gyulai N, et al. Exhaled biomarkers in lung cancer. Eur Respir J, 2009, 34(1): 261-275.
25. Capone S, Tufariello M, Forleo A, et al. Chromatographic analysis of VOC patterns in exhaled breath from smokers and nonsmokers. Biomed Chromatogr, 2018, 32(4).
26. Alonso M, Castellanos M, Sanchez JM. Evaluation of potential breath biomarkers for active smoking: assessment of smoking habits. Anal Bioanal Chem, 2010, 396(8): 2987-2995.
27. Field JK, Smith RA, Aberle DR, et al. International Association for the Study of Lung Cancer Computed Tomography Screening Workshop 2011 report. J Thorac Oncol, 2012, 7(1): 10-19.
28. Wagnetz U, Menezes RJ, Boerner S, et al. CT screening for lung cancer: implication of lung biopsy recommendations. AJR Am J Roentgenol, 2012, 198(2): 351-358.
29. Di Natale C, Macagnano A, Martinelli E, et al. Lung cancer identification by the analysis of breath by means of an array of non-selective gas sensors. Biosens Bioelectron, 2003, 18(10): 1209-1218.
30. Phillips M, Altorki N, Austin JH, et al. Detection of lung cancer using weighted digital analysis of breath biomarkers. Clin Chim Acta, 2008, 393(2): 76-84.

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Identification and diagnostic value of characteristic volatile organic compounds in exhaled breath of patients with early stage lung cancer

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