Analysis of volatile organic compounds from patients and cell lines for the validation of lung cancer biomarkers by proton-transfer-reaction mass spectrometry

Abstract

Exhaled breath from 60 volunteers (20 adenocarcinoma lung cancer (LC) patients, 10 squamous cell carcinoma LC patients, and 30 healthy people) was analyzed using proton-transfer-reaction mass spectrometry (PTR-MS). The Mann–Whitney U test and stepwise forward linear discriminant analysis (LDA) were performed for data analysis. By applying LDA, it was possible to discriminate these three groups. Compared to the healthy group, five characteristic masses (m/z 43, 45, 59, 60 and 61) were found for adenocarcinoma LC and three characteristic masses (m/z 45, 46, and 59) were found in the squamous cell carcinoma group. The diagnostic test parameters for LC detection in the healthy controls were found to be better when more masses were used in comparison to a single mass. In addition, two types of LC cells (A549 and H1703) were used. The VOCs in the headspace of these cultured cells were analyzed to correlate with the production of the VOCs in the breath. Among the characteristic ions in the exhaled breath of LC patients, only m/z 45 was significantly elevated in the headspace of A549 and H1703 cells. We speculate that LC may have an effect on certain metabolic activities, which may also be an important origin of the characteristic markers in the exhaled breath of LC patients. In general, the analysis of VOCs from adenocarcinoma and squamous cell carcinoma LC patients, as well as squamous cell carcinoma and adenocarcinoma cell lines, can help us identify cancer biomarkers. Moreover, it provides a good foundation for studying the origin of biomarkers and their metabolic mechanisms.