title: The expression of four genes as a prognostic classifier for stage I lung adenocarcinoma in 12 independent cohorts.
abstract: BACKGROUND
  We previously developed a prognostic classifier using the expression levels of BRCA1, HIF1A, DLC1, and XPO1 that identified stage I lung adenocarcinoma patients with a high risk of relapse. That study evaluated patients in five independent cohorts from various regions of the world. In an attempt to further validate the classifier, we have used a meta-analysis-based approach to study 12 cohorts consisting of 1,069 tumor-node-metastasis stage I lung adenocarcinoma patients from every suitable, publically available dataset.
  
  
  METHODS
  Cohorts were obtained through a systematic search of public gene expression datasets. These data were used to calculate the risk score using the previously published 4-gene risk model. A fixed effect meta-analysis model was used to generate a pooled estimate for all cohorts.
  
  
  RESULTS
  The classifier was associated with prognosis in 10 of the 12 cohorts (P < 0.05). This association was highly consistent regardless of the ethnic diversity or microarray platform. The pooled estimate demonstrated that patients classified as high risk had worse overall survival for all stage I [HR, 2.66; 95% confidence interval (CI), 1.93-3.67; P < 0.0001] patients and in stratified analyses of stage IA (HR, 2.69; 95% CI, 1.66-4.35; P < 0.0001) and stage IB (HR, 2.69; 95% CI, 1.74-4.16; P < 0.0001) patients.
  
  
  CONCLUSIONS
  The 4-gene classifier provides independent prognostic stratification of stage IA and stage IB patients beyond conventional clinical factors.
  
  
  CONCLUSIONS
  Our results suggest that the 4-gene classifier may assist clinicians in decisions about the postoperative management of early-stage lung adenocarcinoma patients.
authors.affiliation: Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Okayama
authors.affiliation: Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland.
authors.forename: Aaron J
authors.initials: AJ
authors.lastname: Schetter
authors.affiliation: Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland.
authors.forename: Teruhide
authors.initials: T
authors.lastname: Ishigame
authors.affiliation: Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland.
authors.forename: Ana I
authors.initials: AI
authors.lastname: Robles
authors.affiliation: Division of Genome Biology, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kohno
authors.affiliation: Genomics and Epigenomics of Cancer Prediction Program, Institute of Predictive and Personalized Medicine of Cancer, Barcelona, Spain.
authors.forename: Jun
authors.initials: J
authors.lastname: Yokota
authors.affiliation: Department of Organ Regulatory Surgery, Fukushima Medical University School of Medicine, Fukushima, Japan.
authors.forename: Seiichi
authors.initials: S
authors.lastname: Takenoshita
authors.affiliation: Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland. Curtis_Harris@nih.gov.
authors.forename: Curtis C
authors.initials: CC
authors.lastname: Harris
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D000077192:Adenocarcinoma of Lung; D014408:Biomarkers, Tumor / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D009367:Neoplasm Staging; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor