title: Metabolic profiling of potential lung cancer biomarkers using bronchoalveolar lavage fluid and the integrated direct infusion/ gas chromatography mass spectrometry platform.
abstract: Lung cancer is one of the ten most common causes of death worldwide, so that the search for early diagnosis biomarkers is a very challenging task. Bronchoalveolar lavage fluid (BALF) provides information on cellular and biochemical epithelial surface of the lower respiratory tract constituents and no previous metabolomic studies have been performed with BALF samples from patients with lung cancer. Therefore, this fluid has been explored looking for new contributions in lung cancer metabolism. In this way, two complementary metabolomics techniques based on direct infusion high resolution mass spectrometry (DI-ESI-QTOF-MS) and gas chromatography mass spectrometry (GC-MS) have been applied to compare statistically differences between lung cancer (LC) and control (C) BALF samples, using partial least square discriminant analysis (PLS-DA) in order to find and identify potential biomarkers of the disease. A total of 42 altered metabolites were found in BALF from LC. The metabolic pathway analysis showed that glutamate and glutamine metabolism pathway was mainly altered by this disease. In addition, we assessed the biomarker specificity and sensitivity according to the area under the receiver operator characteristic (ROC) curves, indicating that glycerol and phosphoric acid were potential sensitive and specific biomarkers for lung cancer diagnosis and prognosis.
  
  
  
  The search for early diagnosis of lung cancer is a very challenging task because of the high mortality associated to this disease and its critical linkage to the initiation of treatment. Bronchoalveolar lavage fluid provides information on cellular and biochemical epithelial surface of the lower respiratory tract constituents and no previous metabolomic studies have been performed with BALF samples from patients with lung cancer. Since BALF is in close interaction with lung tissue it is a more representative sample of lung status than other peripheral biofluids as blood or urine studied in previous works. Therefore, this study represents an innovative contribution in this topic that complement previous investigations about lung cancer, opening up new possibilities for understanding the pathogenesis of this disease and the use of efficient biomarkers. Therefore, this fluid has been explored looking for new contributions in lung cancer metabolism. In this way, two complementary metabolomic techniques based on direct infusion high resolution mass spectrometry (DI-ESI-QTOF-MS) and gas chromatography mass spectrometry (GC-MS) have been applied to compare statistically significant differences between lung cancer (LC) and control (C) BALF samples, using partial least square discriminant analysis (PLS-DA) in order to find and identify potential biomarkers of the disease. A total of 42 altered metabolites were found in BALF from LC. The metabolic pathway analysis showed that glutamate and glutamine metabolism pathway was mainly altered by this disease. In addition, we assessed the biomarker specificity and sensitivity according to the area under the receiver operator characteristic (ROC) curves, indicating that glycerol and phosphoric acid were potential sensitive and specific biomarkers for lung cancer diagnosis and prognosis.
authors.affiliation: Department of Chemistry, Faculty of Experimental Sciences, University of Huelva, Campus de El Carmen, 21007, Huelva, Spain; International Agrofood Campus of Excellence International ceiA3, University of Huelva, Spain; Research Center of Health and Environment (CYSMA), University of Huelva, Campus de El Carmen, 21007, Huelva, Spain.
authors.forename: Belén
authors.initials: B
authors.lastname: Callejón-Leblic
authors.affiliation: Department of Chemistry, Faculty of Experimental Sciences, University of Huelva, Campus de El Carmen, 21007, Huelva, Spain; International Agrofood Campus of Excellence International ceiA3, University of Huelva, Spain; Research Center of Health and Environment (CYSMA), University of Huelva, Campus de El Carmen, 21007, Huelva, Spain. Electronic address: tamara@dqcm.uhu.es.
authors.forename: Tamara
authors.initials: T
authors.lastname: García-Barrera
authors.affiliation: Pneumonology Area of Juan Ramón Jiménez Hospital, Huelva, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Grávalos-Guzmán
authors.affiliation: Pneumonology Area of Juan Ramón Jiménez Hospital, Huelva, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Pereira-Vega
authors.affiliation: Department of Chemistry, Faculty of Experimental Sciences, University of Huelva, Campus de El Carmen, 21007, Huelva, Spain; International Agrofood Campus of Excellence International ceiA3, University of Huelva, Spain; Research Center of Health and Environment (CYSMA), University of Huelva, Campus de El Carmen, 21007, Huelva, Spain. Electronic address: ariza@uhu.es.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Gómez-Ariza
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D016022:Case-Control Studies; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D005990:Glycerol / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D008297:Male; D053858:Metabolic Networks and Pathways; D055432:Metabolomics / Q000379:methods*; D008875:Middle Aged; D010756:Phosphoric Acids / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D010756:Phosphoric Acids; C030242:phosphoric acid; D005990:Glycerol
keywords: Biomarkers; Bronchoalveolar fluid; Direct infusion mass spectrometry; Gas chromatography mass spectrometry; Lung cancer; Metabolomics