Quantitative breath analysis of volatile organic compounds of lung cancer patients
Introduction
Lung cancer is the most common kind of cancer in the world. In China, lung cancer has an incidence of 26/100,000, and compared to gastric, liver and breast cancer, it is the leading cause of cancer death [1], [2]. The 5-year survival rate for the patients with lung cancer is disappointing. To improve the overall survival, many screening methods including chest radiography, sputum cytology, low-dose spiral computer tomography, fluorescence bronchoscopy and positron emission tomography have been used [3], [4], [5], [6], while these procedures seem to be complicated and expensive.
In 1971, Pauling et al. [7] reported a new method to analyze the VOCs in human breath which shed light on developing new methods of early diagnosis. VOCs are the products of oxidative stress, which can cause peroxidative damage to protein, polyunsaturated fatty acids and DNA in the cells [8], [9], [10]. The peroxidative damage to DNA may be carcinogenic [11], [12]. In some cancers, oxidative stress seems to be increased [13]. VOCs derived from the blood are excreted through the lung by diffusing across the pulmonary alveolar membrane. Some VOCs were identified as markers for the diseases, such as hexane, methylpentane, isoprene and benzene [14], [15]. Nevertheless, breath analysis has taken a long time to be a useful tool because of the lack of standardized breath collecting methods and the low concentrations of VOCs which are present in nanomolar (10−9 mol) or picomolar (10−12 mol) [16]. Phillips et al. [17], [18], [19], [20] developed a breath collecting apparatus to determine VOCs in breath and selected nine VOCs to distinguish patients with lung cancer and normal controls. As a new, simple pre-concentration technique, SPME was developed and widely used in breath analysis [21], [22], [23]. So far, many VOCs have been identified in breath samples of normal human and patients with lung cancer, and a combination of some VOCs is able to discriminate patients. Nevertheless, these VOCs confirmed in above studies were not constant, and the published studies did not concern the relationship of the VOCs concentrations of patients with the histology of lung cancer, such as squamous cell carcinoma and adenocarcinoma.
Previous studies showed that breath analysis might improve the sensitivity and specificity of lung cancer diagnosis in Europe and USA, while the lung cancer susceptibilities and genetic mutations in East Asian were much different from those in the West. For example, the genotype CYP1A1 MSPIC might be one of the susceptibly genetic markers of lung cancer [24], [25] and mutations of the epidermal growth factor receptor gene EGFR were found more frequently in East Asian patients [26], [27]. Study should be done for lack of statistical analysis of VOCs concentrations in the breath of lung cancer patients in China. In the present work, we tried to apply the methodology of SPME with GC/MS to the breath analysis of lung cancer patients in China. The differences of VOCs levels in the lung cancer patients with different stages or histology were also investigated.
Section snippets
Reagents and instruments
The standards (purity >99.5%) of 1-butanol and 3-hydroxy-2-butanone were purchased from Guangfu Research Institute, Tianjin, China. Solid phase micro-extraction manual holder and the fiber of 75 μm carboxen-polydimethylsiloxane (CAR-PDMS) were ordered from Ampel Company, Shanghai, China. 4-l Tedlar® gas bags were bought from Delin Company, Dalian, China. GC/MS-QP 2010 Puls equipped with NIST 05 library was the product of Shimadzu, Japan. The Rxi™–5MS column (30 m, 0.25 mm i.d., 0.25 μm thick) was
Precision and linearity
The method validations including precision and linearity were investigated in the study. The R.S.D. (n = 6) values for 1-butanol and 3-hydroxy-2-butanone were 5.04% and 3.25%, respectively. The linearity and regression equation for 1-butanol are y = 5.22 × 104x − 4.17 × 104 (y: the peak area of 1-butanol; x: the concentration of 1-butanol), r2 = 0.996, respectively. The linearity and regression equation for 3-hydroxy-2-butanone are y = 5.81 × 104x − 1.81 × 105 (y: the peak area of 3-hydroxy-2-butanone; x: the
Discussion
In the past years some studies had demonstrated the uncommon compositions of the breath of the patients suffering from lung cancer. As a non-invasive diagnostic method, breath analysis was of great interest for early lung cancer detection. The results of our study confirmed that the breath of patients with lung cancer was different from that of the healthy. The concentrations of 1-butanol and 3-hydroxy-2-butanone were much higher in the patients’ breath.
In the present study, a simple and
Conclusions
The study shows that SPME with GC/MS is a sensitive and reliable method for discerning the VOCs in human breath. Significant differences were found between the breath of the subjects with or without lung cancer, although the number of the subjects was relatively small, 1-Butanol and 3-hydroxy-2-butanone were considered as potential biomarkers in the breath for lung cancer. VOCs levels might not have any relationship with the different stages of lung cancer patients. Lung adenocarcinoma was
Conflict of interest
We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled, “Quantitative breath analysis of volatile organic compounds of lung cancer patients”.
References (37)
- et al.
The trend of cancer incidence in urban Beijing from 1982 to 1997
China Oncol
(2001) - et al.
Usefulness of positron emission tomography-computed tomography in respiratory medicine
Arch Bronconeumol
(2007) The beginning of the end: IkappaB kinase (IKK) and NF-kappaB activation
Biol Chem
(1999)- et al.
Lipid peroxidation-induced DNA damage in cancer-prone inflammatory diseases: a review of published adduct types and levels in humans
Free Radic Biol Med
(2007) - et al.
Volatile organic compounds in breath as markers of lung cancer: a cross-sectional study
Lancet
(1999) - et al.
Detection of lung cancer with volatile markers in the breath
Chest
(2003) - et al.
Detection of substituted benzenes in water at the pg/ml level using solid-phase microextraction and gas chromatography-ion trap mass spectrometry
J Chromatogr
(1992) - et al.
Investigation of volatile biomarkers in lung cancer blood using solid-phase microextraction and caplillary gas chromatography–mass spectrometry
J Chromatogr B
(2004) - et al.
An analysis of cancer mortality from 1990 to 2002 in Zhejiang Province
China Oncol
(2004) - et al.
Lung cancer screening with sputum cytologic examination, chest radiography, and computed tomography: an update for the U.S. preventive services task force
Ann Intern Med
(2004)
Low-dose CT: a useful and accessible tool for the early diagnosis of lung cancer
Lung Cancer
Autofluorescence bronchoscopy, a novel modality for the early detection of bronchial premalignant and malignant lesions
J Med Invest
Quantitative analysis of urine vapor and breath by gas–liquid partition chromatography
Proc Natl Acad Sci USA
The potential of the hydrocarbon breath test as a measure of lipid peroxidation
Free Radic Biol Med
Oxyradicals and DNA damage
Carcinogenesis
Effect of oxygen on breath markers of oxidative stress
Eur Respir J
Diet and oxidative stress in breast, colon and prostate cancer patients: a case-control study
Eur J Clin Nutr
Volatile organic compounds in exhaled air from patients with lung cancer
Clin Chem
Cited by (210)
Unlocking the secrets: Volatile Organic Compounds (VOCs) and their devastating effects on lung cancer
2024, Pathology Research and PracticeEnhanced sensitivity of a fluorometric biosensor for alcohol metabolites with an enzymatic cycling reaction
2024, Sensors and Actuators B: ChemicalResearch progress of semiconductor metal oxides-based gas sensors towards metabolic gas of Listeria monocytogenes: A mini review
2023, Materials Science in Semiconductor ProcessingLossy mode resonance based 1-butanol sensor in the mid-infrared region
2023, Sensors and Actuators B: Chemical