title: A multigene assay is prognostic of survival in patients with early-stage lung adenocarcinoma.
abstract: OBJECTIVE
  Clinical staging does not adequately risk stratify patients with early stage non-small cell lung cancer. We sought to generate a real-time PCR (RT-PCR)-based prognostic model in patients with early stage lung adenocarcinoma, the dominant histology of lung cancer in the United States.
  
  
  METHODS
  We studied gene expression of 61 candidate genes in 107 patients with completely surgically resected lung adenocarcinoma using RT-PCR. We used crossvalidation methods to select and validate a prognostic model based on the expression of a limited number of genes. A risk score was generated based on model coefficients, and survival of patients with high- and low-risk scores were analyzed.
  
  
  RESULTS
  We generated a four-gene model based on expression of WNT3a, ERBB3, LCK, and RND3. Risk score predicted mortality better than clinical stage or tumor size (adjusted hazard ratio, 6.7; 95% confidence interval, 1.6-28.9; P=0.001). Among 70 patients with stage I disease, 5-year overall survival was 87% among patients with low-risk scores, and 38% among patients with high-risk scores (P=0.0002). Among all patients, 5-year overall survival was 62% and 41%, respectively (P=0.0054). Disease-free survival was also significantly different among low- and high-risk score patients.
  
  
  CONCLUSIONS
  This multigene assay predicts overall and disease-free survival significantly better than clinical stage and tumor size in patients with early stage lung adenocarcinoma and performs especially well in patients with stage I disease. Prospective clinical trials are needed to determine whether high-risk patients with stage I disease benefit from adjuvant chemotherapy.
authors.affiliation: Thoracic Oncology Program, Department of Surgery, University of California, San Francisco, San Francisco, California 94131, USA. Dan.raz@ucsf.edu
authors.forename: Dan J
authors.initials: DJ
authors.lastname: Raz
authors.forename: M Roshni
authors.initials: MR
authors.lastname: Ray
authors.forename: Jae Y
authors.initials: JY
authors.lastname: Kim
authors.forename: Biao
authors.initials: B
authors.lastname: He
authors.forename: Miquel
authors.initials: M
authors.lastname: Taron
authors.forename: Marcin
authors.initials: M
authors.lastname: Skrzypski
authors.forename: Mark
authors.initials: M
authors.lastname: Segal
authors.forename: David R
authors.initials: DR
authors.lastname: Gandara
authors.forename: Rafael
authors.initials: R
authors.lastname: Rosell
authors.forename: David M
authors.initials: DM
authors.lastname: Jablons