Discrimination of cancerous and non-cancerous cell lines by headspace-analysis with PTR-MS

Abstract

Proton transfer reaction mass spectrometry (PTR-MS) has been used to analyze the volatile organic compounds (VOCs) emitted by in-vitro cultured human cells. For this purpose, two pairs of cancerous and non-cancerous human cell lines were selected:1. lung epithelium cells A-549 and retinal pigment epithelium cells hTERT-RPE1, cultured in different growth media; and 2. squamous lung carcinoma cells EPLC and immortalized human bronchial epithelial cells BEAS2B, cultured in identical growth medium. The VOCs in the headspace of the cell cultures were sampled: 1. online by drawing off the gas directly from the culture flask; and 2. by accumulation of the VOCs in PTFE bags connected to the flask for at least 12 h. The pure media were analyzed in the same way as the corresponding cells in order to provide a reference. Direct comparison of headspace VOCs from flasks with cells plus medium and from flasks with pure medium enabled the characterization of cell-line-specific production or consumption of VOCs. Among all identified VOCs in this respect, the most outstanding compound was m/z = 45 (acetaldehyde) revealing significant consumption by the cancerous cell lines but not by the non-cancerous cells. By applying multivariate statistical analysis using 42 selected marker VOCs, it was possible to clearly separate the cancerous and non-cancerous cell lines from each other.

Volatile metabolomic signature of human breast cancer cell lines

“…After applying LDA with backward removal (p < 0.05) of variables, only two VOCs proved to be significant for discrimination between three defined previously, namely 1,2,4-trimethylbenzene and benzaldehyde. These compounds have been already identified in cancer cell studies by Brunner et al 29. using PTR-MS, by Filipiak et al 16.…”

Detection of Volatile Malodorous Compounds in Breath: Current Analytical Techniques and Implications in Human Disease

“…Results of studying different lung cancer cell lines in 2D cultures suggested that altered VOC production can be detected in the early stages of carcinogenesis, and can represent a basis for noninvasive diagnosis of lung cancer. Therefore, 2D studies on various normal or cancer cell lines showed either an increase or decrease in several volatile compounds classes such as alkanes, aldehydes, aromatic compounds or alcohols [25, [165][166][167][168][169][170][171][172]. A recent study uses both cancerous and noncancerous lung cell lines grown in 3D scaffolds of collagen type I hydrogel [167].…”

Rapid Identification of Cancerous Cell Lines and Evaluation of Cytotoxic Effects on Cancer Cells with VUV-PIMS

“…Thus, the VOC profiles under cytotoxic exposure were measured. Polyphyllin belongs to the antimitotic class of agents which can promote tubulin polymerization and is now widely used to treat a range of malignancies (19)(20)(21). Vitamin C was also included in this study as a positive control compound as it is always used in chemotherapy for its antioxidant (22,23).…”

“…However, it should be collocated with electrosurgical devices and measuring it production of "smoke", which means characterization can't be made unless the electrosurgical knife has cut down. Proton transfer reaction mass spectrometry (PTR-MS) was also carried out for online and offline characterization of VOC biomarkers from cancer cells [19]. Nevertheless, the detected VOC biomarkers were limited to molecules with a proton affinity greater than that of water [20], among which there were not extremely specific cancer-related VOCs observed by the online measurement of PTR-MS.…”