Development and validation of a prognostic gene-expression signature for lung adenocarcinoma

Cited 30 time in scopus
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Title
Development and validation of a prognostic gene-expression signature for lung adenocarcinoma
Author(s)
Y Y Park; E S Park; S B Kim; Sang Cheol Kim; B H Sohn; In-Sun Chu; W Jeong; G B Mills; L A Byers; J S Lee
Bibliographic Citation
PLoS One, vol. 7, no. 9, pp. e44225-e44225
Publication Year
2012
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.
ISSN
1932-6203
Publisher
Public Library of Science
DOI
http://dx.doi.org/10.1371/journal.pone.0044225
Type
Article
Appears in Collections:
Division of Biomedical Research > Metabolic Regulation Research Center > 1. Journal Articles
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