title: Combined sputum hypermethylation and eNose analysis for lung cancer diagnosis.
abstract: OBJECTIVE
  The aim of this study is to explore DNA hypermethylation analysis in sputum and exhaled breath analysis for their complementary, non-invasive diagnostic capacity in lung cancer.
  
  
  METHODS
  Sputum samples and exhaled breath were prospectively collected from 20 lung cancer patients and 31 COPD controls (Set 1). An additional 18 lung cancer patients and 8 controls only collected exhaled breath as validation set (Set 2). DNA hypermethylation of biomarkers RASSF1A, cytoglobin, APC, FAM19A4, PHACTR3, 3OST2 and PRDM14 was considered, and breathprints from exhaled breath samples were created using an electronic nose (eNose).
  
  
  RESULTS
  Both DNA hypermethylation markers in sputum and eNose were independently able to distinguish lung cancer patients from controls. The combination of RASSF1A and 3OST2 hypermethylation had a sensitivity of 85% with a specificity of 74%. eNose had a sensitivity of 80% with a specificity of 48%. Sensitivity for lung cancer diagnosis increased to 100%, when RASSF1A hypermethylation was combined with eNose, with specificity of 42%. Both methods showed to be complementary to each other (p≤0.011). eNose results were reproducible in Set 2.
  
  
  CONCLUSIONS
  When used in concert, RASSF1A hypermethylation in sputum and exhaled breath analysis are complementary for lung cancer diagnosis, with 100% sensitivity in this series. This finding should be further validated.
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: A Jasmijn
authors.initials: AJ
authors.lastname: Hubers
authors.affiliation: Department of Respiratory Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Paul
authors.initials: P
authors.lastname: Brinkman
authors.affiliation: Department of Respiratory Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Remco J
authors.initials: RJ
authors.lastname: Boksem
authors.affiliation: Department of Respiratory Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Rhodius
authors.affiliation: Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Birgit I
authors.initials: BI
authors.lastname: Witte
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Aeilko H
authors.initials: AH
authors.lastname: Zwinderman
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Daniëlle A M
authors.initials: DA
authors.lastname: Heideman
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Duin
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Remco
authors.initials: R
authors.lastname: Koning
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Renske D M
authors.initials: RD
authors.lastname: Steenbergen
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Peter J F
authors.initials: PJ
authors.lastname: Snijders
authors.affiliation: Department of Pulmonary Diseases, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Egbert F
authors.initials: EF
authors.lastname: Smit
authors.affiliation: Department of Respiratory Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Sterk
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Erik
authors.initials: E
authors.lastname: Thunnissen
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D001944:Breath Tests; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D008297:Male; D012680:Sensitivity and Specificity; D013183:Sputum / Q000737:chemistry*
chemical_list: D014408:Biomarkers, Tumor
keywords: DIAGNOSTICS; GENETICS; LUNG CANCER; MOLECULAR ONCOLOGY; SPUTUM