Filipiak Wojciech, Filipiak Anna, Sponring Andreas, Schmid Thomas, Zelger Bettina, Ager Clemens, Klodzinska Ewa, Denz Hubert, Pizzini Alex, Lucciarini Paolo, Jamnig Herbert, Troppmair Jakob, Amann Anton
Breath Research Institute of the University of Innsbruck, A-6850 Dornbirn, Austria. Univ.-Clinic for Anesthesia and Intensive Care, Innsbruck Medical University, A-6020 Innsbruck, Austria.
J Breath Res. 2014 Jun;8(2):027111. doi: 10.1088/1752-7155/8/2/027111. Epub 2014 May 27.
Breath analysis for the purpose of non-invasive diagnosis of lung cancer has yielded numerous candidate compounds with still questionable clinical relevance. To arrive at suitable volatile organic compounds our approach combined the analysis of different sources: isolated tumor samples compared to healthy lung tissues, and exhaled breath from lung cancer patients and healthy controls. Candidate compounds were further compared to substances previously identified in the comparison of transformed and normal lung epithelial cell lines. For human studies, a breath sampling device was developed enabling automated and CO2-controlled collection of the end-tidal air. All samples were first preconcentrated on multibed sorption tubes and analyzed with gas chromatography mass spectrometry (GC-MS). Significantly (p < 0.05) higher concentrations in all three types of cancer samples studied were observed for ethanol and n-octane. Additional metabolites (inter alia 2-methylpentane, n-hexane) significantly released by lung cancer cells were observed at higher levels in cancer lung tissues and breath samples (compared to respective healthy controls) with statistical significance (p < 0.05) only in breath samples. The results obtained confirmed the cancer-related origin of volatile metabolites, e.g. ethanol and octane that were both detected at significantly (p < 0.05) elevated concentrations in all three kinds of cancer samples studied. This work is an important step towards identification of volatile breath markers of lung cancer through the demonstration of cancer-related origin of certain volatile metabolites.
用于肺癌非侵入性诊断的呼吸分析已产生了许多具有临床相关性仍存疑问的候选化合物。为了找到合适的挥发性有机化合物，我们的方法结合了对不同来源的分析：将分离出的肿瘤样本与健康肺组织进行比较，以及对肺癌患者和健康对照者的呼出气体进行分析。候选化合物还与之前在转化的和正常的肺上皮细胞系比较中鉴定出的物质进行了进一步比较。对于人体研究，开发了一种呼吸采样装置，能够自动且在二氧化碳控制下收集终末潮气。所有样本首先在多床吸附管上进行预浓缩，然后用气相色谱 - 质谱联用仪（GC - MS）进行分析。在所有研究的三种癌症样本中，观察到乙醇和正辛烷的浓度显著（p < 0.05）更高。在肺癌组织和呼吸样本中观察到肺癌细胞显著释放的其他代谢物（特别是2 - 甲基戊烷、正己烷）水平更高，仅在呼吸样本中具有统计学意义（p < 0.05）。所获得的结果证实了挥发性代谢物的癌症相关来源，例如乙醇和辛烷，在所有研究的三种癌症样本中均检测到其浓度显著（p < 0.05）升高。这项工作通过证明某些挥发性代谢物的癌症相关来源，朝着识别肺癌的挥发性呼吸标志物迈出了重要一步。
