非小细胞肺癌患者呼气中挥发性有机化合物的定量分析

Quantitative analysis of volatile biomarkers in breath of non-small cell lung cancer patients

目的：通过对非小细胞肺癌患者呼出气体中的挥发性有机化合物进行定量检测，评价挥发性有机化舍物对非小细胞肺癌诊断的意义。方法：用Tedlar采样袋收集43份非小细胞肺癌患者和41份正常人的呼气样品，经固相微萃取浓缩后，用气相色谱／质谱检测呼气中的挥发性有机化合物，结果用外标法定量。通过ROC曲线评价呼气分析诊断非小细胞肺癌的临床价值，对早期和晚期非小细胞肺癌以及肺腺癌和鳞癌之间的呼气分析差异进行统计学分析。结果：在非小细胞肺癌患者呼气中正丁醇和3-羟基-2-丁酮的浓度分别为6．36和8．28ng／L，明显高于正常人呼气中的浓度，P〈0．001。正丁醇和3-羟基-2-丁酮作为挥发性标志在Ⅰ～Ⅱ期非小细胞肺癌患者呼气中的浓度和Ⅲ～Ⅳ期进行比较，差异无统计学意义（P〉0．05），而它们在肺腺癌患者的呼气中的浓度高于鳞癌患者，P〈0．05。结论：正丁醇和3-羟基-2-丁酮可作为肺癌呼气诊断的挥发性标志，可能对非小细胞肺癌的腺、鳞癌鉴别诊断有帮助，但不能作为早晚期肺癌的鉴别指标。

OBJECTIVE： By the quantitative analysis of the volatile organic compounds （VOCs） in human breath to evaluate the clinical significance of VOCs in patients with non small cell lung cancer. METH： ODS： The breath samples were collected from 43 patients with nonsmall cell lung cancer （NSCLC） and 41 normal controls by using Tedlar gas bags. 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 by using the external standard 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： In the breath of the patients the median concentrations of 1-butanol and 3-hydroxy-2-butanone were 6.36 and 8.28 ng/L, respectively, which were significantly higher than those in the controls （P〈0. 001）. No significant differences were observed between the patients with stage Ⅰ - Ⅱ and stage Ⅲ-- Ⅳ （P〉0.05）. Lung adenoearcinoma was significantly related to higher VOCs coneen trations compared to those in the breath of lung squamous cell carcinoma patients （P〈0.05）. CONCLUSIONS： 1-Butanol and 3-hydroxy 2-buta none in breath are significantly related to lung cancer, which can be taken as useful breath biomarkers for discerning potential lung cancer patients, especially for discerning lung adenocarcinoma from lung squamous cell carcinoma. These markers can not discern the different stages of lung cancer.