title: Sputum microRNA profiling: a novel approach for the early detection of non-small cell lung cancer.
abstract: OBJECTIVE
  MicroRNAs (miRNAs) post-transcriptionally regulate hundreds of gene targets involved in tumorigenesis thereby controlling vital biological processes, including cellular proliferation, differentiation and apoptosis. MiRNA profiling is an emerging tool for the potential early detection of a variety of malignancies. This study was conducyed to assess the feasibility and methodological robustness of quantifying sputum miRNAs, employing quantitative real-time polymerase chain reaction (RT-qPCR) and cluster analysis on an optimized miRNA profile as a novel approach for the early detection of non-small cell lung cancer (NSCLC).
  
  
  METHODS
  The relative expressions of 11 miRNAs in sputum (miR-21, miR-145, miR-155, miR-205, miR-210, miR-92, miR-17-5p, miR-143, miR-182, miR-372, and let-7a) in addition to U6 were retrospectively assessed in four NSCLC-positive and four negative controls. Subsequently, a set of five miRNAs (miR-21, miR-143, miR-155, miR-210, miR-372) was selected because of degree of relatedness observed in the cluster analysis and tested in the same sputum sample set. The five optimized miRNAs accurately clustered these eight retrospective patients into NSCLC positive cases and negative controls. The five miRNA panel was then prospectively quantified in the sputum of 30 study patients (24 NSCLC cases and six negative controls) in a double-blind fashion to validate a five miRNA panel using hierarchical cluster analysis.
  
  
  RESULTS
  The optimized five miRNA panel detected NSCLC (83.3% sensitivity and 100% specificity) in 30 prospectively accrued study patients.
  
  
  CONCLUSIONS
  Sputum miRNA profiling using cluster analysis is a promising approach for the early detection of non-small cell lung cancer. Further investigation using this approach is warranted.
authors.affiliation: Department of Oncology, Cross Cancer Institute and University of Alberta, Edmonton, Alberta, Canada. wilson.roa@albertahealthservices.ca
authors.forename: Wilson H
authors.initials: WH
authors.lastname: Roa
authors.forename: Julian O
authors.initials: JO
authors.lastname: Kim
authors.forename: Rene
authors.initials: R
authors.lastname: Razzak
authors.forename: Hongfei
authors.initials: H
authors.lastname: Du
authors.forename: Linghong
authors.initials: L
authors.lastname: Guo
authors.forename: Ravinder
authors.initials: R
authors.lastname: Singh
authors.forename: Sayf
authors.initials: S
authors.lastname: Gazala
authors.forename: Sunita
authors.initials: S
authors.lastname: Ghosh
authors.forename: Eric
authors.initials: E
authors.lastname: Wong
authors.forename: Anil A
authors.initials: AA
authors.lastname: Joy
authors.forename: James Z
authors.initials: JZ
authors.lastname: Xing
authors.forename: Eric L
authors.initials: EL
authors.lastname: Bedard
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000235:genetics; D004311:Double-Blind Method; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000235:genetics; D008297:Male; D035683:MicroRNAs / Q000032:analysis / Q000235:genetics*; D008875:Middle Aged; D011446:Prospective Studies; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D013183:Sputum / Q000737:chemistry*
chemical_list: C542359:MIRN143 microRNA, human; C524942:MIRN155 microRNA, human; C524940:MIRN21 microRNA, human; C543800:MIRN210 microRNA, human; C561021:MIRN372 microRNA, human; D035683:MicroRNAs