title: Development and validation of a prognostic gene-expression signature for lung adenocarcinoma.
abstract: Although several prognostic signatures have been developed in lung cancer, their application in clinical practice has been limited because they have not been validated in multiple independent data sets. Moreover, the lack of common genes between the signatures makes it difficult to know what biological process may be reflected or measured by the signature. By using classical data exploration approach with gene expression data from patients with lung adenocarcinoma (n = 186), we uncovered two distinct subgroups of lung adenocarcinoma and identified prognostic 193-gene gene expression signature associated with two subgroups. The signature was validated in 4 independent lung adenocarcinoma cohorts, including 556 patients. In multivariate analysis, the signature was an independent predictor of overall survival (hazard ratio, 2.4; 95% confidence interval, 1.2 to 4.8; p = 0.01). An integrated analysis of the signature revealed that E2F1 plays key roles in regulating genes in the signature. Subset analysis demonstrated that the gene signature could identify high-risk patients in early stage (stage I disease), and patients who would have benefit of adjuvant chemotherapy. Thus, our study provided evidence for molecular basis of clinically relevant two distinct two subtypes of lung adenocarcinoma.
authors.affiliation: Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Yun-Yong
authors.initials: YY
authors.lastname: Park
authors.forename: Eun Sung
authors.initials: ES
authors.lastname: Park
authors.forename: Sang Bae
authors.initials: SB
authors.lastname: Kim
authors.forename: Sang Cheol
authors.initials: SC
authors.lastname: Kim
authors.forename: Bo Hwa
authors.initials: BH
authors.lastname: Sohn
authors.forename: In-Sun
authors.initials: IS
authors.lastname: Chu
authors.forename: Woojin
authors.initials: W
authors.lastname: Jeong
authors.forename: Gordon B
authors.initials: GB
authors.lastname: Mills
authors.forename: Lauren Averett
authors.initials: LA
authors.lastname: Byers
authors.forename: Ju-Seog
authors.initials: JS
authors.lastname: Lee
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017024:Chemotherapy, Adjuvant; D016000:Cluster Analysis; D015331:Cohort Studies; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D015999:Multivariate Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D015203:Reproducibility of Results; D016019:Survival Analysis; D059467:Transcriptome