title: Cell-free DNA levels in plasma of patients with non-small-cell lung cancer and inflammatory lung disease.
abstract: BACKGROUND
  The analysis of plasma cell-free DNA (cfDNA) is expected to provide useful biomarkers for early diagnosis of non-small-cell lung cancer (NSCLC). However, it remains unclear whether the intense release of cfDNA into the bloodstream of NSCLC patients results from malignancy or chronic inflammatory response. Consequently, the current diagnostic utility of plasma cfDNA quantification has not been thoroughly validated in subjects with chronic respiratory inflammation. Here we assess the effect of chronic respiratory inflammation on plasma cfDNA levels and evaluate the potential clinical value of this phenomenon as an early lung cancer diagnostic tool.
  
  
  METHODS
  We measured plasma cfDNA concentrations in 50 resectable NSCLC patients, 101 patients with chronic respiratory inflammation (chronic obstructive pulmonary disease, sarcoidosis, or asthma) and 40 healthy volunteers using real-time PCR.
  
  
  RESULTS
  We found significantly higher plasma cfDNA levels in NSCLC patients than in subjects with chronic respiratory inflammation and healthy individuals (P<0.0001). There were no significant differences in plasma cfDNA levels between patients with chronic respiratory inflammation and healthy volunteers. The cutoff point of >2.8 ng ml(-1) provided 90% sensitivity and 80.5% specificity in discriminating NSCLC from healthy individuals (area under the curve (AUC)=0.90). The receiver-operating characteristics curve distinguishing NSCLC patients from subjects with chronic respiratory inflammation indicated 56% sensitivity and 91% specificity at the >5.25-ng ml(-1) cutoff (AUC=0.76).
  
  
  CONCLUSIONS
  We demonstrated that elevated plasma cfDNA levels in NSCLC resulted primarily from tumour development rather than inflammatory response, raising the potential clinical implications for lung cancer screening and early diagnosis. Further research is necessary to better characterise and identify factors and processes regulating cfDNA levels in the blood under normal and pathological conditions.
authors.affiliation: Department of Genetics and Clinical Immunology, National Institute of Tuberculosis and Lung Diseases, 26 Plocka Street, 01-138 Warsaw, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Szpechcinski
authors.affiliation: Department of Genetics and Clinical Immunology, National Institute of Tuberculosis and Lung Diseases, 26 Plocka Street, 01-138 Warsaw, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Chorostowska-Wynimko
authors.affiliation: Department of Genetics and Clinical Immunology, National Institute of Tuberculosis and Lung Diseases, 26 Plocka Street, 01-138 Warsaw, Poland.
authors.forename: R
authors.initials: R
authors.lastname: Struniawski
authors.affiliation: Department of Thoracic Surgery, National Institute of Tuberculosis and Lung Diseases, 26 Plocka Street, 01-138 Warsaw, Poland.
authors.forename: W
authors.initials: W
authors.lastname: Kupis
authors.affiliation: Department of Thoracic Surgery, National Institute of Tuberculosis and Lung Diseases, 26 Plocka Street, 01-138 Warsaw, Poland.
authors.forename: P
authors.initials: P
authors.lastname: Rudzinski
authors.affiliation: Department of Pathomorphology, National Institute of Tuberculosis and Lung Diseases, 26 Plocka Street, 01-138 Warsaw, Poland.
authors.forename: R
authors.initials: R
authors.lastname: Langfort
authors.affiliation: II Department of Lung Diseases, National Institute of Tuberculosis and Lung Diseases, 26 Plocka Street, 01-138 Warsaw, Poland.
authors.forename: E
authors.initials: E
authors.lastname: Puscinska
authors.affiliation: IV Department of Lung Diseases, National Institute of Tuberculosis and Lung Diseases, 26 Plocka Street, 01-138 Warsaw, Poland.
authors.forename: P
authors.initials: P
authors.lastname: Bielen
authors.affiliation: IV Department of Lung Diseases, National Institute of Tuberculosis and Lung Diseases, 26 Plocka Street, 01-138 Warsaw, Poland.
authors.forename: P
authors.initials: P
authors.lastname: Sliwinski
authors.affiliation: Department of Thoracic Surgery, National Institute of Tuberculosis and Lung Diseases, 26 Plocka Street, 01-138 Warsaw, Poland.
authors.forename: T
authors.initials: T
authors.lastname: Orlowski
mesh_terms: D000230:Adenocarcinoma / Q000097:blood* / Q000175:diagnosis; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood* / Q000175:diagnosis; D002908:Chronic Disease; D004247:DNA / Q000097:blood*; D003937:Diagnosis, Differential; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood* / Q000175:diagnosis; D008297:Male; D008875:Middle Aged; D011014:Pneumonia / Q000097:blood* / Q000175:diagnosis
chemical_list: D004247:DNA