title: Multiple marker detection in peripheral blood for NSCLC diagnosis.
abstract: BACKGROUND
  Non-invasive early detection of lung cancer could reduce the number of patients diagnosed with advanced disease, which is associated with a poor prognosis. We analyzed the diagnostic accuracy of a panel of peripheral blood markers in detecting non small cell lung cancer (NSCLC).
  
  
  METHODS
  100 healthy donors and 100 patients with NSCLC were enrolled onto this study. Free circulating DNA, circulating mRNA expression of peptidylarginine deiminase type 4 (PAD4/PADI4), pro-platelet basic protein (PPBP) and haptoglobin were evaluated using a Real-Time PCR-based method.
  
  
  RESULTS
  Free circulating DNA, PADI4, PPBP and haptoglobin levels were significantly higher in NSCLC patients than in healthy donors (p<0.0001, p<0.0001, p=0.0002 and p=0.0001, respectively). The fitted logistic regression model demonstrated a significant direct association between marker expression and lung cancer risk. The odds ratios of individual markers were 6.93 (95% CI 4.15-11.58; p<0.0001) for free DNA, 6.99 (95% CI 3.75-13.03; p<0.0001) for PADI4, 2.85 (95% CI 1.71-4.75; p<0.0001) for PPBP and 1.16 (95% CI 1.01-1.33; p=0.031) for haptoglobin. Free DNA in combination with PPBP and PADI4 gave an area under the ROC curve of 0.93, 95% CI=0.90-0.97, with sensitivity and specificity over 90%.
  
  
  CONCLUSIONS
  Free circulating DNA analysis combined with PPBP and PADI4 expression determination appears to accurately discriminate between healthy donors and NSCLC patients. This non-invasive multimarker approach warrants further research to assess its potential role in the diagnostic or screening workup of subjects with suspected lung cancer.
authors.affiliation: Biosciences Laboratory, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola, Italy. p.ulivi@irst.emr.it
authors.forename: Paola
authors.initials: P
authors.lastname: Ulivi
authors.forename: Laura
authors.initials: L
authors.lastname: Mercatali
authors.forename: Gian-Luca
authors.initials: GL
authors.lastname: Casoni
authors.forename: Emanuela
authors.initials: E
authors.lastname: Scarpi
authors.forename: Lauro
authors.initials: L
authors.lastname: Bucchi
authors.forename: Rosella
authors.initials: R
authors.lastname: Silvestrini
authors.forename: Stefano
authors.initials: S
authors.lastname: Sanna
authors.forename: Marco
authors.initials: M
authors.lastname: Monteverde
authors.forename: Dino
authors.initials: D
authors.lastname: Amadori
authors.forename: Venerino
authors.initials: V
authors.lastname: Poletti
authors.forename: Wainer
authors.initials: W
authors.lastname: Zoli
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood*; D008297:Male; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor