title: Unique volatolomic signatures of TP53 and KRAS in lung cells.
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.
authors: Molecular and Clinical Cancer Medicine, University of Liverpool, Cancer Research Centre, 200 London Road, Liverpool, L3 9TA, UK.
authors: M P A
authors: MP
authors: Davies
authors: Department of Chemical Engineering, Technion-Israel Institute of Technology, Haifa 32000, Israel.
authors: O
authors: O
authors: Barash
authors: Department of Chemical Engineering, Technion-Israel Institute of Technology, Haifa 32000, Israel.
authors: R
authors: R
authors: Jeries
authors: Tel-Aviv University and Thoracic Cancer Research and Detection Center, Sheba Medical Center, Tel Hashomer 52621, Israel.
authors: N
authors: N
authors: Peled
authors: Tel-Aviv University and Thoracic Cancer Research and Detection Center, Sheba Medical Center, Tel Hashomer 52621, Israel.
authors: M
authors: M
authors: Ilouze
authors: Molecular and Clinical Cancer Medicine, University of Liverpool, Cancer Research Centre, 200 London Road, Liverpool, L3 9TA, UK.
authors: R
authors: R
authors: Hyde
authors: Molecular and Clinical Cancer Medicine, University of Liverpool, Cancer Research Centre, 200 London Road, Liverpool, L3 9TA, UK.
authors: M W
authors: MW
authors: Marcus
authors: Molecular and Clinical Cancer Medicine, University of Liverpool, Cancer Research Centre, 200 London Road, Liverpool, L3 9TA, UK.
authors: J K
authors: JK
authors: Field
authors: Department of Chemical Engineering, Technion-Israel Institute of Technology, Haifa 32000, Israel.
authors: H
authors: H
authors: Haick
mesh_terms: D000388:Air / Q000032:analysis; D001185:Artificial Intelligence; D001980:Bronchi; D002478:Cells, Cultured; D016002:Discriminant Analysis; D004847:Epithelial Cells / Q000378:metabolism*; D008401:Gas Chromatography-Mass Spectrometry; D055785:Gene Knockdown Techniques; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D046228:Microarray Analysis; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D055549:Volatile Organic Compounds / Q000032:analysis*; D018631:ras Proteins / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; D055549:Volatile Organic Compounds; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins