Comparison of volatile organic compounds from lung cancer patients and healthy controls-challenges and limitations of an observational study
Comparison of volatile organic compounds from lung cancer patients and healthy controls-challenges and limitations of an observational study
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DOI：
10.1088/1752-7155/10/4/046007
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发表时间：
2016-12-01
影响因子：
3.8
通讯作者：
Nehls, Irene
中科院分区：
文献类型：
--
作者：
Schallschmidt, Kristin;Becker, Roland;Nehls, Irene
本文概述了对37名肺癌患者和23名年龄相仿的健康对照者呼吸中挥发性有机化合物（VOCs）的观察性研究的设计和性能。需要量化每个VOC被认为是一个潜在的疾病标志物的基础上，个人校准的阐述，和质量控制措施，以保持呼吸采样和随后的仪器痕量VOC分析，使用固相微萃取-气相色谱-质谱在14个月的研究期间的再现性进行了描述。24种挥发性有机化合物被量化的基础上，他们以前建议的潜在的癌症标志物。正如预期的那样，吸烟者呼吸中芳香族化合物的浓度增加，而肺癌患者显示出显着增加的含氧VOC水平，如醛，2-丁酮和1-丁醇。尽管使用留一交叉验证的线性判别分析（LDA），所选含氧VOC的集合显示出80%至90%的灵敏度和特异性，但呼吸VOC方法在癌症检测方面的有效选择性显然是有限的。结果进行了讨论的挥发性癌症标志物的调查和前景的文献的背景下，病人的呼吸与方法，采用嗅探犬的VOC水平增加。本研究和文献的经验表明，目前可用的方法无法使用呼吸VOC可靠地区分癌症患者和健康对照。观察性研究往往倾向于注意到某些含氧VOC水平的显着差异，但没有实际应用所需的分辨率。任何利用VOC特征差异进行疾病检测的步骤都必须解决目前由低浓度和可变VOC浓度设定的限制。进一步的挑战是涉及呼吸采样的研究的技术复杂性，以及当前分析程序检测不稳定标记候选物的能力可能有限。
This paper outlines the design and performance of an observational study on the profiles of volatile organic compounds (VOCs) in the breath of 37 lung cancer patients and 23 healthy controls of similar age. The need to quantify each VOC considered as a potential disease marker on the basis of individual calibration is elaborated, and the quality control measures required to maintain reproducibility in breath sampling and subsequent instrumental trace VOC analysis using solid phase microextraction-gas chromatography-mass spectrometry over a study period of 14 months are described. Twenty-four VOCs were quantified on the basis of their previously suggested potential as cancer markers. The concentration of aromatic compounds in the breath was increased, as expected, in smokers, while lung cancer patients displayed significantly increased levels of oxygenated VOCs such as aldehydes, 2-butanone and 1-butanol. Although sets of selected oxygenated VOCs displayed sensitivities and specificities between 80% and 90% using linear discriminant analysis (LDA) with leave-one-out cross validation, the effective selectivity of the breath VOC approach with regard to cancer detection is clearly limited. Results are discussed against the background of the literature on volatile cancer marker investigations and the prospects of linking increased VOC levels in patients' breath with approaches that employ sniffer dogs. Experience from this study and the literature suggests that the currently available methodology is not able to use breath VOCs to reliably discriminate between cancer patients and healthy controls. Observational studies often tend to note significant differences in levels of certain oxygenated VOCs, but without the resolution required for practical application. Any step towards the exploitation of differences in VOC profiles for illness detection would have to solve current restrictions set by the low and variable VOC concentrations. Further challenges are the technical complexity of studies involving breath sampling and possibly the limited capability of current analytical procedures to detect unstable marker candidates.