Skip Navigation LinksHome > August 2007 - Volume 2 - Issue 8 > Proliferation and ‘invasiveness’ gene-expression signatures...
Journal of Thoracic Oncology:
doi: 10.1097/01.JTO.0000283287.58693.11
Proffered Paper Abstracts: Session D6: Molecular Biology & Prognostic Factors, Thursday, September 6: Molecular Biology & Prognostic Factors, Thu, 12:30 - 14:15

Proliferation and ‘invasiveness’ gene-expression signatures predict survival of surgically treated non-small-cell lung cancer: D6-03

Starmans, Maud H.1; Krisnapuram, Balaji2; Steck, Harald2; Seigneuric, Renaud1; Buffa, Francesca M.3; Harris, Adrian L.3; De Ruysscher, Dirk1; Wouters, Bradly G.1; Lambin, Philippe1

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1Maastricht Radioation Oncology (Maastro), GROW Research Institute, University of Maastricht, Maastricht, The Netherlands 2Siemens Medical Solutions, Philadelphia, PA, USA 3Weatherhall Institute of Molecular Medicine, University of Oxford, Oxford, UK

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Introduction:

Non-small cell lung cancer (NSCLC) is a leading cause of cancer mortality in both men and women. One way to improve the outcome is to predict survival at diagnosis, in order to select patients for the most appropriate treatment. As microarray data have already shown to be able to predict the outcome, we hypothesized that further refining the prognostic value of these profiles would be possible by selecting them according to biological characteristics such as proliferation and hypoxia.

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Methods:

Several in vitro derived published and unpublished gene-expression based signatures were tested on a clinical patient microarray dataset. This dataset consists of 86 surgically treated NSCLC patients of which complete follow-up data was available.

The previously published wound signature, invasiveness gene signature (IGS) and Chi signature (hypoxia) as well as an unpublished signature for proliferation were evaluated with a signature score. This score was defined as the weighted average expression of the genes in the signature. This score is used to evaluate the predictive accuracy of the various signatures based on Kaplan-Meier survival analysis, log-rank tests and multivariate Cox-regression analysis.

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Results:

Only two of the evaluated signatures, IGS and proliferation signature, had significant predictive value in Kaplan-Meier survival analyses. Stratifying patients in groups based on the score of these signatures resulted in a clear difference in survival, p-values of log-rank test were 0.039 and 0.018 for the IGS and proliferation signature respectively. The areas under the curves for 2-years survival were 0.64 for the IGS and 0.66 for the proliferation signature. Further multivariate Cox-regression analysis with backward stepwise selection procedure showed that the proliferation signature was the only signature that was an independent predictive parameter (p = 0.030).

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Conclusions:

The proliferation signature is a predictor for survival of surgically treated patients with NSCLC in univariate and multivariate analysis, while the IGS was only significant in univariate analysis. This information may further enable the selection of patients for adjuvant therapy as well as give further insight to the mechanisms underlying the bad prognosis.

Copyright © 2007 by the European Lung Cancer Conference and the International Association for the Study of Lung Cancer.

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