ABSTRACT
BACKGROUND: Volatile organic compounds (VOCs) are potential biomarkers for cancer detection in breath, but it is unclear if they reflect specific mutations. To test this, we have compared human bronchial epithelial cell (HBEC) cell lines carrying the KRAS(V12) mutation, knockdown of TP53 or both with parental HBEC cells. METHODS: VOC from headspace above cultured cells were collected by passive sampling and analysed by thermal desorption gas chromatography mass spectrometry (TD-GC-MS) or sensor array with discriminant factor analysis (DFA). RESULTS: In TD-GC-MS analysis, individual compounds had limited ability to discriminate between cell lines, but by applying DFA analysis combinations of 20 VOCs successfully discriminated between all cell types (accuracies 80-100%, with leave-one-out cross validation). Sensor array detection DFA demonstrated the ability to discriminate samples based on their cell type for all comparisons with accuracies varying between 77% and 93%. CONCLUSIONS: Our results demonstrate that minimal genetic changes in bronchial airway cells lead to detectable differences in levels of specific VOCs identified by TD-GC-MS or of patterns of VOCs identified by sensor array output. From the clinical aspect, these results suggest the possibility of breath analysis for detection of minimal genetic changes for earlier diagnosis or for genetic typing of lung cancers.
Subject(s)
Epithelial Cells/metabolism , Lung Neoplasms/genetics , Proto-Oncogene Proteins/genetics , Tumor Suppressor Protein p53/genetics , Volatile Organic Compounds/analysis , ras Proteins/genetics , Air/analysis , Artificial Intelligence , Bronchi , Cells, Cultured , Discriminant Analysis , Gas Chromatography-Mass Spectrometry , Gene Knockdown Techniques , Humans , Microarray Analysis , Mutation , Proto-Oncogene Proteins p21(ras)ABSTRACT
Exact results are derived concerning quasiregularity and diffusion of strong chaos on resonances of the sawtooth map. A chaotic ensemble of well-defined quasiregularity type (the sequence of resonances visited) is generally a fractal set whose main characteristics, the topological entropy and the Hausdorff dimension, are calculated exactly, under some conditions, using a symbolic dynamics. The effect of quasiregularity on chaotic diffusion is characterized by an infinity of diffusion coefficients, each associated with a fractal ensemble trapped in a periodic set of resonances. In some cases, these coefficients are calculated exactly and it is shown that rigorous diffusion takes place on the resonances.
