title: Stratification of resectable lung adenocarcinoma by molecular and pathological risk estimators.
abstract: BACKGROUND
  Mortality in early stage, resectable lung cancer is sufficiently high to warrant consideration of post-surgical treatment. Novel markers to stratify resectable lung cancer patients may help with the selection of treatment to improve outcome.
  
  
  METHODS
  Primary tumour tissue from 485 patients, surgically treated for stage I-II lung adenocarcinoma, was analysed for the RNA expression of 31 cell cycle progression (CCP) genes by quantitative polymerase chain reaction (PCR). The expression average, the CCP score, was combined with pathological stage into a prognostic score (PS). Cox proportional hazards regression assessed prediction of 5-year lung cancer mortality above clinical variables. The PS threshold was tested for risk discrimination by the Mantel-Cox log-rank test.
  
  
  RESULTS
  The CCP score added significant information above clinical markers (all patients, P=0.0029; stage I patients, P=0.013). The prognostic score was a superior predictor of outcome compared to pathological stage alone (PS, P=0.00084; stage, P=0.24). Five-year lung cancer mortality was significantly different between the low-risk (90%, 95% confidence interval (CI) 81-95%), and high-risk groups (65%, 95% CI 57-72%), P=4.2×10(-6)).
  
  
  CONCLUSIONS
  The CCP score is an independent prognostic marker in early stage lung adenocarcinoma. The prognostic score provides superior risk estimates than stage alone. The threefold higher risk in the high-risk group defines a subset of patients that should consider therapeutic choices to improve outcome.
authors.affiliation: Division of Cancer and Stem Cells, School of Medicine, The University of Nottingham, Nottingham NG7 2RD, UK; The Nottingham Health Science Biobank (NHSB), Nottingham University Hospitals NHS Trust, Nottingham NG7 2RD, UK. Electronic address: Emad.Rakha@nottingham.ac.uk.
authors.forename: Emad
authors.initials: E
authors.lastname: Rakha
authors.affiliation: Program in Solid Tumor and Biomarkers, Center for Applied Medical Research, University of Navarra, Pamplona 31008, Spain.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Pajares
authors.affiliation: Centre Hospitalier Universitaire de Nice, Louis Pasteur Hospital, Laboratory of Clinical and Experimental Pathology, Hospital-Integrated Biobank, University of Nice Sophia Antipolis, Nice 06003, France.
authors.forename: Marius
authors.initials: M
authors.lastname: Ilie
authors.affiliation: Program in Solid Tumor and Biomarkers, Center for Applied Medical Research, University of Navarra, Pamplona 31008, Spain.
authors.forename: Ruben
authors.initials: R
authors.lastname: Pio
authors.affiliation: Department of Pathology, Clínica Universidad de Navarra, Pamplona, Spain.
authors.forename: Jose
authors.initials: J
authors.lastname: Echeveste
authors.affiliation: Myriad Genetics, Inc., Salt Lake City, UT 84108, USA.
authors.forename: Elisha
authors.initials: E
authors.lastname: Hughes
authors.affiliation: Department of Pathology, Nottingham University Hospitals, Nottingham NG7 2RD, UK.
authors.forename: Irshad
authors.initials: I
authors.lastname: Soomro
authors.affiliation: Centre Hospitalier Universitaire de Nice, Louis Pasteur Hospital, Laboratory of Clinical and Experimental Pathology, Hospital-Integrated Biobank, University of Nice Sophia Antipolis, Nice 06003, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Long
authors.affiliation: Department of Pathology, Clínica Universidad de Navarra, Pamplona, Spain.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Idoate
authors.affiliation: Myriad Genetics, Inc., Salt Lake City, UT 84108, USA.
authors.forename: Susanne
authors.initials: S
authors.lastname: Wagner
authors.affiliation: Myriad Genetics, Inc., Salt Lake City, UT 84108, USA.
authors.forename: Jerry S
authors.initials: JS
authors.lastname: Lanchbury
authors.affiliation: Department of Respiratory Medicine, Nottingham University Hospitals, Nottingham NG5 1PB, UK.
authors.forename: David R
authors.initials: DR
authors.lastname: Baldwin
authors.affiliation: Centre Hospitalier Universitaire de Nice, Louis Pasteur Hospital, Laboratory of Clinical and Experimental Pathology, Hospital-Integrated Biobank, University of Nice Sophia Antipolis, Nice 06003, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Hofman
authors.affiliation: Program in Solid Tumor and Biomarkers, Center for Applied Medical Research, University of Navarra, Pamplona 31008, Spain.
authors.forename: Luis M
authors.initials: LM
authors.lastname: Montuenga
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D000077192:Adenocarcinoma of Lung; D014408:Biomarkers, Tumor / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics*; D003661:Decision Support Techniques; D005060:Europe; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D008297:Male; D009367:Neoplasm Staging; D011013:Pneumonectomy; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D015203:Reproducibility of Results; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins
keywords: Expression signature; Lung adenocarcinoma; Post-surgical treatment; Prognostic marker