title: Validation of a proliferation-based expression signature as prognostic marker in early stage lung adenocarcinoma.
abstract: OBJECTIVE
  New prognostic markers to guide treatment decisions in early stage non-small cell lung cancer are necessary to improve patient outcomes. In this report, we assess the utility of a predefined mRNA expression signature of cell-cycle progression genes (CCP score) to define 5-year risk of lung cancer-related death in patients with early stage lung adenocarcinoma.
  
  
  METHODS
  A CCP score was calculated from the mRNA expression levels of 31 proliferation genes in stage I and stage II tumor samples from two public microarray datasets [Director's Consortium (DC) and GSE31210]. The same gene set was tested by quantitative PCR in 381 formalin-fixed paraffin-embedded (FFPE) primary tumors. Association of the CCP score with outcome was assessed by Cox proportional hazards analysis.
  
  
  RESULTS
  In univariate analysis, the CCP score was a strong predictor of cancer-specific survival in both the Director's Consortium cohort (P = 0.00014; HR = 2.08; 95% CI, 1.43-3.02) and GSE31210 (P = 0.0010; HR = 2.25; 95% CI, 1.42-3.56). In multivariate analysis, the CCP score remained the dominant prognostic marker in the presence of clinical variables (P = 0.0022; HR = 2.02; 95% CI, 1.29-3.17 in Director's Consortium, P = 0.0026; HR = 2.16; 95% CI, 1.32-3.53 in GSE31210). On a quantitative PCR platform, the CCP score maintained highly significant prognostic value in FFPE-derived mRNA from clinical samples in both univariate (P = 0.00033; HR = 2.10; 95% CI, 1.39-3.17) and multivariate analyses (P = 0.0071; HR = 1.92; 95% CI, 1.18-3.10).
  
  
  CONCLUSIONS
  The CCP score is a significant predictor of lung cancer death in early stage lung adenocarcinoma treated with surgery and may be a valuable tool in selecting patients for adjuvant treatment.
authors.affiliation: Authors' Affiliations: Departments of Translational Molecular Pathology, Thoracic/Head and Neck, Pathology, and Thoracic and Cardiovascular Surgery, The University of Texas, MD Anderson Cancer Center, Houston, Texas; Myriad Genetics, Inc., Salt Lake City, Utah; and Istituto Europeo di Oncologia, Milan, Italy.
authors.forename: Ignacio I
authors.initials: II
authors.lastname: Wistuba
authors.forename: Carmen
authors.initials: C
authors.lastname: Behrens
authors.forename: Francesca
authors.initials: F
authors.lastname: Lombardi
authors.forename: Susanne
authors.initials: S
authors.lastname: Wagner
authors.forename: Junya
authors.initials: J
authors.lastname: Fujimoto
authors.forename: M Gabriela
authors.initials: MG
authors.lastname: Raso
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Spaggiari
authors.forename: Domenico
authors.initials: D
authors.lastname: Galetta
authors.forename: Robyn
authors.initials: R
authors.lastname: Riley
authors.forename: Elisha
authors.initials: E
authors.lastname: Hughes
authors.forename: Julia
authors.initials: J
authors.lastname: Reid
authors.forename: Zaina
authors.initials: Z
authors.lastname: Sangale
authors.forename: Steven G
authors.initials: SG
authors.lastname: Swisher
authors.forename: Neda
authors.initials: N
authors.lastname: Kalhor
authors.forename: Cesar A
authors.initials: CA
authors.lastname: Moran
authors.forename: Alexander
authors.initials: A
authors.lastname: Gutin
authors.forename: Jerry S
authors.initials: JS
authors.lastname: Lanchbury
authors.forename: Massimo
authors.initials: M
authors.lastname: Barberis
authors.forename: Edward S
authors.initials: ES
authors.lastname: Kim
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality* / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D002453:Cell Cycle; D049109:Cell Proliferation; D017024:Chemotherapy, Adjuvant; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000401:mortality* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000096:biosynthesis; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger
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