title: Serum phosphatidylethanolamine levels distinguish benign from malignant solitary pulmonary nodules and represent a potential diagnostic biomarker for lung cancer.
abstract: BACKGROUND
  Recent computed tomography (CT) screening trials showed that it is effective for early detection of lung cancer, but were plagued by high false positive rates. Additional blood biomarker tests designed to complement CT screening and reduce false positive rates are highly desirable.
  
  
  OBJECTIVE
  Identify blood-based metabolite biomarkers for diagnosing lung cancer.
  
  
  METHODS
  Serum samples from subjects participating in a CT screening trial were analyzed using untargeted GC-TOFMS and HILIC-qTOFMS-based metabolomics. Samples were acquired prior to diagnosis (pre-diagnostic, n= 17), at-diagnosis (n= 25) and post-diagnosis (n= 19) of lung cancer and from subjects with benign nodules (n= 29).
  
  
  RESULTS
  Univariate analysis identified 40, 102 and 30 features which were significantly different between subjects with malignant (pre-, at- and post-diagnosis) solitary pulmonary nodules (SPNs) and benign SPNs, respectively. Ten metabolites were consistently different between subjects presenting malignant (pre- and at-diagnosis) or benign SPNs. Three of these 10 metabolites were phosphatidylethanolamines (PE) suggesting alterations in lipid metabolism. Accuracies of 77%, 83% and 78% in the pre-diagnosis group and 69%, 71% and 67% in the at-diagnosis group were determined for PE(34:2), PE(36:2) and PE(38:4), respectively.
  
  
  CONCLUSIONS
  This study demonstrates evidence of early metabolic alterations that can possibly distinguish malignant from benign SPNs. Further studies in larger pools of samples are warranted.
authors.affiliation: University of California, Davis Genome Center, Davis, California, CA, USA.
authors.forename: Johannes F
authors.initials: JF
authors.lastname: Fahrmann
authors.affiliation: CDS Creative Data Solutions, Ballwin, MO, USA.
authors.forename: Dmitry
authors.initials: D
authors.lastname: Grapov
authors.affiliation: University of California, Davis Genome Center, Davis, California, CA, USA.
authors.forename: Brian C
authors.initials: BC
authors.lastname: DeFelice
authors.affiliation: Division of Biostatistics, Department of Public Health Sciences, School of Medicine, University of California, Davis, California, CA, USA.
authors.forename: Sandra
authors.initials: S
authors.lastname: Taylor
authors.affiliation: Division of Biostatistics, Department of Public Health Sciences, School of Medicine, University of California, Davis, California, CA, USA.
authors.forename: Kyoungmi
authors.initials: K
authors.lastname: Kim
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, School of Medicine, University of California, Davis Medical Center, Sacramento, CA, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Kelly
authors.affiliation: University of California, Davis Genome Center, Davis, California, CA, USA.
authors.forename: William R
authors.initials: WR
authors.lastname: Wikoff
authors.affiliation: Division of Thoracic Surgery, Department of Cardiothoracic Surgery, Langone Medical Center, New York University, New York, NY, USA.
authors.forename: Harvey
authors.initials: H
authors.lastname: Pass
authors.affiliation: Division of Pulmonary, Critical Care, and Sleep, NYU School of Medicine, New York, NY, USA.
authors.forename: William N
authors.initials: WN
authors.lastname: Rom
authors.affiliation: University of California, Davis Genome Center, Davis, California, CA, USA.|Department of Biochemistry, Faculty of Sciences, King Abdulaziz University, Jeddah, Saudi-Arabia.
authors.forename: Oliver
authors.initials: O
authors.lastname: Fiehn
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, School of Medicine, University of California, Davis Medical Center, Sacramento, CA, USA.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Miyamoto
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood* / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D008297:Male; D055442:Metabolome; D055432:Metabolomics / Q000379:methods; D008875:Middle Aged; D009367:Neoplasm Staging; D010714:Phosphatidylethanolamines / Q000097:blood*; D012372:ROC Curve; D003074:Solitary Pulmonary Nodule / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D010714:Phosphatidylethanolamines; C483858:phosphatidylethanolamine
keywords: Lung cancer; biomarkers; metabolomics; phospholipids; solitary pulmonary nodules