title: Detection of Lung Cancer through Metabolic Changes Measured in Blood Plasma.
abstract: BACKGROUND
  Low-dose computed tomography, the currently used tool for lung cancer screening, is characterized by a high rate of false-positive results. Accumulating evidence has shown that cancer cell metabolism differs from that of normal cells. Therefore, this study aims to evaluate whether the metabolic phenotype of blood plasma allows detection of lung cancer.
  
  
  METHODS
  The proton nuclear magnetic resonance spectrum of plasma is divided into 110 integration regions, representing the metabolic phenotype. These integration regions reflect the relative metabolite concentrations and were used to train a classification model in discriminating between 233 patients with lung cancer and 226 controls. The validity of the model was examined by classifying an independent cohort of 98 patients with lung cancer and 89 controls.
  
  
  RESULTS
  The model makes it possible to correctly classify 78% of patients with lung cancer and 92% of controls, with an area under the curve of 0.88. Important moreover is the fact that the model is convincing, which is demonstrated by validation in the independent cohort with a sensitivity of 71%, a specificity of 81%, and an area under the curve of 0.84. Patients with lung cancer have increased glucose and decreased lactate and phospholipid levels. The limited number of patients in the subgroups and their heterogeneous nature do not (yet) enable differentiation between histological subtypes and tumor stages.
  
  
  CONCLUSIONS
  Metabolic phenotyping of plasma allows detection of lung cancer, even in an early stage. Increased glucose and decreased lactate levels are pointing to an increased gluconeogenesis and are in accordance with recently published findings. Furthermore, decreased phospholipid levels confirm the enhanced membrane synthesis.
authors.affiliation: Faculty of Medicine and Life Sciences, Hasselt University, Hasselt, Belgium.
authors.forename: Evelyne
authors.initials: E
authors.lastname: Louis
authors.affiliation: Biomolecule Design Group, Institute for Materials Research, Hasselt University, Hasselt, Belgium; Applied and Analytical Chemistry, Institute for Materials Research, Hasselt University, Hasselt, Belgium.
authors.forename: Peter
authors.initials: P
authors.lastname: Adriaensens
authors.affiliation: Biomolecule Design Group, Institute for Materials Research, Hasselt University, Hasselt, Belgium.
authors.forename: Wanda
authors.initials: W
authors.lastname: Guedens
authors.affiliation: Interuniversity Institute for Biostatistics and statistical Bioinformatics, Hasselt University, Hasselt, Belgium.
authors.forename: Theophile
authors.initials: T
authors.lastname: Bigirumurame
authors.affiliation: Janssen Diagnostics BVBA, Beerse, Belgium.
authors.forename: Kurt
authors.initials: K
authors.lastname: Baeten
authors.affiliation: Faculty of Medicine and Life Sciences, Hasselt University, Hasselt, Belgium; Department of Respiratory Medicine, Algemeen Ziekenhuis Vesalius, Tongeren, Belgium.
authors.forename: Karolien
authors.initials: K
authors.lastname: Vanhove
authors.affiliation: Department of Respiratory Medicine, Mariaziekenhuis Noord-Limburg, Overpelt, Belgium.
authors.forename: Kurt
authors.initials: K
authors.lastname: Vandeurzen
authors.affiliation: Department of Respiratory Medicine, Ziekenhuis Maas en Kempen, Maaseik, Belgium.
authors.forename: Karen
authors.initials: K
authors.lastname: Darquennes
authors.affiliation: Department of Respiratory Medicine, Universitaire Ziekenhuizen Katholieke Universiteit Leuven, Leuven, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: Vansteenkiste
authors.affiliation: Department of Respiratory Medicine, Universitaire Ziekenhuizen Katholieke Universiteit Leuven, Leuven, Belgium.
authors.forename: Christophe
authors.initials: C
authors.lastname: Dooms
authors.affiliation: Interuniversity Institute for Biostatistics and statistical Bioinformatics, Hasselt University, Hasselt, Belgium.
authors.forename: Ziv
authors.initials: Z
authors.lastname: Shkedy
authors.affiliation: Faculty of Medicine and Life Sciences, Hasselt University, Hasselt, Belgium; Department of Nuclear Medicine, Ziekenhuis Oost-Limburg, Genk, Belgium.
authors.forename: Liesbet
authors.initials: L
authors.lastname: Mesotten
authors.affiliation: Faculty of Medicine and Life Sciences, Hasselt University, Hasselt, Belgium; Department of Respiratory Medicine, Ziekenhuis Oost-Limburg, Genk, Belgium. Electronic address: michiel.thomeer@uhasselt.be.
authors.forename: Michiel
authors.initials: M
authors.lastname: Thomeer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood; D016022:Case-Control Studies; D015331:Cohort Studies; D055088:Early Detection of Cancer; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood* / Q000175:diagnosis*; D008297:Male; D008660:Metabolism; D008875:Middle Aged
chemical_list: D014408:Biomarkers, Tumor
keywords: (1)H-NMR spectroscopy; Blood plasma biomarker; Lung cancer; Metabolic phenotype; Risk model