title: Differentiation between genetic mutations of breast cancer by breath volatolomics.
abstract: Mapping molecular sub-types in breast cancer (BC) tumours is a rapidly evolving area due to growing interest in, for example, targeted therapy and screening high-risk populations for early diagnosis. We report a new concept for profiling BC molecular sub-types based on volatile organic compounds (VOCs). For this purpose, breath samples were collected from 276 female volunteers, including healthy, benign conditions, ductal carcinoma in situ (DCIS) and malignant lesions. Breath samples were analysed by gas chromatography mass spectrometry (GC-MS) and artificially intelligent nanoarray technology. Applying the non-parametric Wilcoxon/Kruskal-Wallis test, GC-MS analysis found 23 compounds that were significantly different (p < 0.05) in breath samples of BC patients with different molecular sub-types. Discriminant function analysis (DFA) of the nanoarray identified unique volatolomic signatures between cancer and non-cancer cases (83% accuracy in blind testing), and for the different molecular sub-types with accuracies ranging from 82 to 87%, sensitivities of 81 to 88% and specificities of 76 to 96% in leave-one-out cross-validation. These results demonstrate the presence of detectable breath VOC patterns for accurately profiling molecular sub-types in BC, either through specific compound identification by GC-MS or by volatolomic signatures obtained through statistical analysis of the artificially intelligent nanoarray responses.
authors.affiliation: Department of Chemical Engineering and Russel Berrie Nanotechnology Institute, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Orna
authors.initials: O
authors.lastname: Barash
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Anhui, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Chemical Engineering and Russel Berrie Nanotechnology Institute, Technion-Israel Institute of Technology, Haifa, Israel.|Present Address: Department of Chemical Engineering, University of New Hampshire, Durham, NH, USA.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Halpern
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Anhui, China.
authors.forename: Qing-Ling
authors.initials: QL
authors.lastname: Hua
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Anhui, China.
authors.forename: Yue-Yin
authors.initials: YY
authors.lastname: Pan
authors.affiliation: Department of Chemical Engineering and Russel Berrie Nanotechnology Institute, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Haneen
authors.initials: H
authors.lastname: Kayal
authors.affiliation: Department of Chemical Engineering and Russel Berrie Nanotechnology Institute, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Kayan
authors.initials: K
authors.lastname: Khoury
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Anhui, China.
authors.forename: Hu
authors.initials: H
authors.lastname: Liu
authors.affiliation: Molecular & Clinical Cancer Medicine, University of Liverpool, Cancer Research Centre, Liverpool, United Kingdom.
authors.forename: Michael P A
authors.initials: MP
authors.lastname: Davies
authors.affiliation: Department of Chemical Engineering and Russel Berrie Nanotechnology Institute, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Hossam
authors.initials: H
authors.lastname: Haick
mesh_terms: D000328:Adult; D000368:Aged; D001185:Artificial Intelligence; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism*; D001944:Breath Tests / Q000379:methods*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000235:genetics* / Q000378:metabolism*; D016022:Case-Control Studies; D003937:Diagnosis, Differential; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D020022:Genetic Predisposition to Disease; D006801:Humans; D046228:Microarray Analysis; D008875:Middle Aged; D009154:Mutation; D036103:Nanotechnology; D010641:Phenotype; D011237:Predictive Value of Tests; D055549:Volatile Organic Compounds / Q000378:metabolism*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D055549:Volatile Organic Compounds
keywords: breast cancer; molecular; sensor; spectrometry; volatolomic