title: Diagnostic accuracy of MALDI mass spectrometric analysis of unfractionated serum in lung cancer.
abstract: OBJECTIVE
  There is a critical need for improvements in the noninvasive diagnosis of lung cancer. We hypothesized that matrix-assisted laser desorption ionization mass spectrometry (MALDI MS) analysis of the most abundant peptides in the serum may distinguish lung cancer cases from matched controls.
  
  
  METHODS
  We used MALDI MS to analyze unfractionated serum from a total of 288 cases and matched controls split into training (n = 182) and test sets (n = 106). We used a training-testing paradigm with application of the model profile defined in a training set to a blinded test cohort.
  
  
  RESULTS
  Reproducibility and lack of analytical bias was confirmed in quality-control studies. A serum proteomic signature of seven features in the training set reached an overall accuracy of 78%, a sensitivity of 67.4%, and a specificity of 88.9%. In the blinded test set, this signature reached an overall accuracy of 72.6 %, a sensitivity of 58%, and a specificity of 85.7%. The serum signature was associated with the diagnosis of lung cancer independently of gender, smoking status, smoking pack-years, and C-reactive protein levels. From this signature, we identified three discriminatory features as members of a cluster of truncated forms of serum amyloid A.
  
  
  CONCLUSIONS
  We found a serum proteomic profile that discriminates lung cancer from matched controls. Proteomic analysis of unfractionated serum may have a role in the noninvasive diagnosis of lung cancer and will require methodological refinements and prospective validation to achieve clinical utility.
authors.affiliation: Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: Pinar B
authors.initials: PB
authors.lastname: Yildiz
authors.forename: Yu
authors.initials: Y
authors.lastname: Shyr
authors.forename: Jamshedur S M
authors.initials: JS
authors.lastname: Rahman
authors.forename: Noel R
authors.initials: NR
authors.lastname: Wardwell
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Zimmerman
authors.forename: Bashar
authors.initials: B
authors.lastname: Shakhtour
authors.forename: William H
authors.initials: WH
authors.lastname: Gray
authors.forename: Shuo
authors.initials: S
authors.lastname: Chen
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.forename: Heinrich
authors.initials: H
authors.lastname: Roder
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Liebler
authors.forename: William L
authors.initials: WL
authors.lastname: Bigbee
authors.forename: Jill M
authors.initials: JM
authors.lastname: Siegfried
authors.forename: Joel L
authors.initials: JL
authors.lastname: Weissfeld
authors.forename: Adriana L
authors.initials: AL
authors.lastname: Gonzalez
authors.forename: Mathew
authors.initials: M
authors.lastname: Ninan
authors.forename: David H
authors.initials: DH
authors.lastname: Johnson
authors.forename: David P
authors.initials: DP
authors.lastname: Carbone
authors.forename: Richard M
authors.initials: RM
authors.lastname: Caprioli
authors.forename: Pierre P
authors.initials: PP
authors.lastname: Massion
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000473:pathology; D014408:Biomarkers, Tumor / Q000097:blood*; D001798:Blood Proteins / Q000378:metabolism*; D018287:Carcinoma, Large Cell / Q000097:blood / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood* / Q000473:pathology; D018288:Carcinoma, Small Cell / Q000097:blood / Q000473:pathology; D016022:Case-Control Studies; D002853:Chromatography, Liquid; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism; D009367:Neoplasm Staging; D018307:Neoplasms, Squamous Cell / Q000097:blood / Q000473:pathology; D011379:Prognosis; D040901:Proteomics; D012680:Sensitivity and Specificity; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D014408:Biomarkers, Tumor; D001798:Blood Proteins; D009363:Neoplasm Proteins