title: A unique set of 6 circulating microRNAs for early detection of non-small cell lung cancer.
abstract: BACKGROUND
  Circulating microRNAs are promising biomarkers for diagnosis, predication and prognostication of diseases. Lung cancer is the cancer disease accountable for most cancer deaths, largely due to being diagnosed at late stages. Therefore, diagnosing lung cancer patients at an early stage is crucial for improving the outcome. The purpose of this study was to identify circulating microRNAs for detection of early stage lung cancer, capable of discriminating lung cancer patients from those with chronic obstructive pulmonary disease (COPD) and healthy volunteers.
  
  
  RESULTS
  We identified 7 microRNAs separating lung cancer patients from controls. By using RT-qPCR, we validated 6 microRNAs (miR-429, miR-205, miR-200b, miR-203, miR-125b and miR-34b) with a significantly higher abundance in serum from NSCLC patients. Furthermore, the 6 miRNAs were validated in a different dataset, revealing an area under the receiver operating characteristic curve of 0.89 for stage I-IV and 0.88 for stage I/II.
  
  
  METHODS
  We profiled the expression of 754 unique microRNAs by TaqMan Low Density Arrays, and analyzed serum from 38 patients with NSCLC, 16 patients suffering from COPD and 16 healthy volunteers from Norway, to explore their potential as diagnostic biomarkers. For validation, we analyzed serum collected from high-risk individuals enrolled in the Valencia branch of the International Early Lung Cancer Action Program screening trial (n=107) in addition to 51 lung cancer patients.
  
  
  CONCLUSIONS
  Considering the accessibility and stability of circulating miRNAs, these 6 microRNAs are promising biomarkers as a supplement in future screening studies.
authors.affiliation: Department of Cancer Genetics, Institute for Cancer Research, OUS Radiumhospitalet, Oslo, Norway.
authors.forename: Ann Rita
authors.initials: AR
authors.lastname: Halvorsen
authors.affiliation: Department of Cancer Genetics, Institute for Cancer Research, OUS Radiumhospitalet, Oslo, Norway.|Department of Oncology, OUS Radiumhospitalet, Oslo, Norway.
authors.forename: Maria
authors.initials: M
authors.lastname: Bjaanæs
authors.affiliation: Oslo Centre for Biostatistics and Epidemiology, Research Support Services, Oslo University Hospital, Oslo, Norway.
authors.forename: Marissa
authors.initials: M
authors.lastname: LeBlanc
authors.affiliation: Department of Respiratory Medicine, OUS Rikshospitalet, Oslo, Norway.
authors.forename: Are M
authors.initials: AM
authors.lastname: Holm
authors.affiliation: Department of Medical Biochemistry, OUS Radiumhospitalet, Oslo, Norway.
authors.forename: Nils
authors.initials: N
authors.lastname: Bolstad
authors.affiliation: Laboratory of Molecular Biology, Fundación Instituto Valenciano de Oncología, Valencia, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Rubio
authors.affiliation: Department of Thoracic Surgery, Fundación Instituto Valenciano de Oncología, Valencia, Spain.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Peñalver
authors.affiliation: Department of Radiology, Fundación Instituto Valenciano de Oncología, Valencia, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Cervera
authors.affiliation: Department of Pathology, Fundación Instituto Valenciano de Oncología, Valencia, Spain.
authors.forename: Julia Cruz
authors.initials: JC
authors.lastname: Mojarrieta
authors.affiliation: Laboratory of Molecular Biology, Fundación Instituto Valenciano de Oncología, Valencia, Spain.
authors.forename: Jose Antonio
authors.initials: JA
authors.lastname: López-Guerrero
authors.affiliation: Department of Cancer Genetics, Institute for Cancer Research, OUS Radiumhospitalet, Oslo, Norway.|Department of Oncology, OUS Radiumhospitalet, Oslo, Norway.
authors.forename: Odd Terje
authors.initials: OT
authors.lastname: Brustugun
authors.affiliation: Department of Cancer Genetics, Institute for Cancer Research, OUS Radiumhospitalet, Oslo, Norway.|Department of Oncology, OUS Radiumhospitalet, Oslo, Norway.
authors.forename: Åslaug
authors.initials: Å
authors.lastname: Helland
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood* / Q000235:genetics / Q000473:pathology; D000074166:Circulating MicroRNA / Q000097:blood*; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D020869:Gene Expression Profiling; D064368:Healthy Volunteers; D006801:Humans; D008168:Lung / Q000473:pathology; D008175:Lung Neoplasms / Q000097:blood* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009664:Norway; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood*; D012372:ROC Curve; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; D000074166:Circulating MicroRNA
keywords: COPD; biomarker; circulating microRNAs; early detection; lung cancer