Development and Validation of a Prognostic Gene-Expression Signature for Lung Adenocarcinoma

Yun Yong Park, Eun Sung Park, Sang Bae Kim, Sang Cheol Kim, Bo Hwa Sohn, In Sun Chu, Woojin Jeong, Gordon Mills, Lauren Averett Byers, Ju Seog Lee

Research output: Contribution to journalArticle

23 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere44225
JournalPLoS One
Volume7
Issue number9
DOIs
StatePublished - Sep 7 2012
Externally publishedYes

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adenocarcinoma
Transcriptome
Gene expression
Genes
lungs
gene expression
genes
Biological Phenomena
Chemotherapy
lung neoplasms
Adjuvant Chemotherapy
multivariate analysis
drug therapy
adjuvants
confidence interval
Lung Neoplasms
Hazards
Multivariate Analysis
Confidence Intervals
Gene Expression

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Park, Y. Y., Park, E. S., Kim, S. B., Kim, S. C., Sohn, B. H., Chu, I. S., ... Lee, J. S. (2012). Development and Validation of a Prognostic Gene-Expression Signature for Lung Adenocarcinoma. PLoS One, 7(9), [e44225]. https://doi.org/10.1371/journal.pone.0044225

Development and Validation of a Prognostic Gene-Expression Signature for Lung Adenocarcinoma. / Park, Yun Yong; Park, Eun Sung; Kim, Sang Bae; Kim, Sang Cheol; Sohn, Bo Hwa; Chu, In Sun; Jeong, Woojin; Mills, Gordon; Byers, Lauren Averett; Lee, Ju Seog.

In: PLoS One, Vol. 7, No. 9, e44225, 07.09.2012.

Research output: Contribution to journalArticle

Park, YY, Park, ES, Kim, SB, Kim, SC, Sohn, BH, Chu, IS, Jeong, W, Mills, G, Byers, LA & Lee, JS 2012, 'Development and Validation of a Prognostic Gene-Expression Signature for Lung Adenocarcinoma', PLoS One, vol. 7, no. 9, e44225. https://doi.org/10.1371/journal.pone.0044225
Park, Yun Yong ; Park, Eun Sung ; Kim, Sang Bae ; Kim, Sang Cheol ; Sohn, Bo Hwa ; Chu, In Sun ; Jeong, Woojin ; Mills, Gordon ; Byers, Lauren Averett ; Lee, Ju Seog. / Development and Validation of a Prognostic Gene-Expression Signature for Lung Adenocarcinoma. In: PLoS One. 2012 ; Vol. 7, No. 9.
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