Quantitative Analysis Of Trace Volatile Organic Compounds In Breath Of Lung Cancer Patients

Objective To determine and quantitate the volatile organic compounds(VOCs) in the breath of lung cancer patients and normal human.The clinical applicability of analyzing VOCs for diagnosis of lung cancer was assessed.The relationship between VOCs levels with cancer stages and histologies was studied. Methods We collected breath samples from 43 patients with non small cell lung cancer(NSCLC) and 41 normal controls using Tedlar^? gas bags.The VOCs were extracted with solid phase microextraction(SPME) and analyzed by gas chromatography(GC)/mass spectrometry(MS).The concentration of selected VOCs in breath was calculated using standard curve method.The differences of VOCs concentrations in the breath of patients and controls were analyzed.The discriminative power was assessed by receiver operator characteristic(ROC) curve. Statistical analyses were used for assessing the differences of VOCs levels in the lung cancer patients with different stages or histologies.Results The number of VOCs detected in each breath sample ranged from 68 to 114. Among them,the GC peak areas of 1-butanol and 3-hydroxy-2-butanone in the breath of patients were higher than those in the controls.The method provided relative standard deviation(%,R.S.D) values 5.04 for 1-butanol and 3.25 for 3-hydroxy-2-butanone and the linear correlation 0.998 for 1-butanol and 0.994 for 3-hydroxy-2-butanone.In the breath of patients and controls,the median concentrations of 1-butanol were 6.36ng/L and 2.18ng/L,respectively and the median concentrations of 3-hydroxy-2-butanone were 8.28ng/L and 1.29ng/L, respectively.1-Butanol and 3-hydroxy-2-butanone were found at significantly higher concentrations in breath of the lung cancer patients compared to the controls(p＜0.001).Taking 3.67ng/L as cutoff value for 1-butanol,the diagnostic sensitivity was 95.3%and specificity 85.4%.Taking 3.81ng/L as cutoff value for 3-hydroxy-2-butanone,the diagnostic sensitivity was 93.0%and specificity 92.7%.In the breath of patients with stageⅠ～Ⅱand stageⅢ～Ⅳ,the median concentrations of 1-butanol were 9.67ng/L and 5.18ng/L,respectively and the median concentrations of 3-hydroxy-2-butanone were 9.23ng/L and 8.28ng/L,respectively.VOCs levels were not significantly different comparing lung cancer patients with stageⅠ～Ⅱand stageⅢ～Ⅳ(p＞0.05).In the breath of patients with lung adenocarcinoma and lung squamous cell carcinoma,the median concentrations of 1-butanol were 11.63ng/L and 4.70ng/L,respectively and the median concentrations of 3-hydroxy-2-butanone were 13.14ng/L and 6.41ng/L,respectively.Lung adenocarcinoma was significantly related to higher VOCs concentrations in the breath(p＜0.05).Conclusion 1-Butanol and 3-hydroxy-2-butanone in breath were significantly related to lung cancer,which could be taken as useful breath biomarker for discerning potential lung cancer patients,especially for lung adenocarcinoma.Breath analysis might provide a new method for lung cancer diagnosis.