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Gene profiling of clinical routine biopsies and prediction of survival in non-small cell lung cancer

Baty, Florent and Facompré, Michaël and Kaiser, Sergio and Schumacher, Martin and Pless, Miklos and Bubendorf, Lukas and Savic, Spasenija and Marrer, Estelle and Budach, Wolfgang and Buess, Martin and Kehren, Jeanne and Tamm, Michael and Brutsche, Martin H.. (2010) Gene profiling of clinical routine biopsies and prediction of survival in non-small cell lung cancer. American journal of respiratory and critical care medicine, Vol. 181, H. 2. pp. 181-188.

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Official URL: http://edoc.unibas.ch/dok/A6005590

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Abstract

RATIONALE: Global gene expression analysis provides a comprehensive molecular characterization of non-small cell lung cancer (NSCLC). OBJECTIVES: To evaluate the feasibility of integrating expression profiling into routine clinical work-up by including both surgical and minute bronchoscopic biopsies and to develop a robust prognostic gene expression signature. METHODS: Tissue samples from 41 chemotherapy-naive patients with NSCLC and 15 control patients with inflammatory lung diseases were obtained during routine clinical work-up and gene expression profiles were gained using an oligonucleotide array platform (NovaChip; 34'207 transcripts). Gene expression signatures were analyzed for correlation with histological and clinical parameters and validated on independent published data sets and immunohistochemistry. MEASUREMENTS AND MAIN RESULTS: Diagnostic signatures for adenocarcinoma and squamous cell carcinoma reached a sensitivity of 80%/80% and a specificity of 83%/94%, respectively, dependent on the proportion of tumor cells. Sixty-seven of the 100 most discriminating genes were validated with independent observations from the literature. A 13-gene metagene refined on four external data sets was built and validated on an independent data set. The metagene was a strong predictor of survival in our data set (hazard ratio = 7.7, 95% CI [2.8-21.2]) and in the independent data set (hazard ratio = 1.6, 95% CI [1.2-2.2]) and in both cases independent of the International Union against Cancer staging. Vascular endothelial growth factor-beta, one of the key prognostic genes, was further validated by immunohistochemistry on 508 independent tumor samples. CONCLUSIONS: Integration of functional genomics from small bronchoscopic biopsies allows molecular tumor classification and prediction of survival in NSCLC and might become a powerful adjunct for the daily clinical practice.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Pulmonary Cell Research (Roth/Tamm)
03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Ehemalige Einheiten Medizinische Fächer (Klinik) > Onkologie (Herrmann)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Ehemalige Einheiten Medizinische Fächer (Klinik) > Onkologie (Herrmann)
03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Pneumologie
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Pneumologie
03 Faculty of Medicine > Bereich Querschnittsfächer (Klinik) > Pathologie USB > Stammzellpathologie (Bubendorf)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Querschnittsfächer (Klinik) > Pathologie USB > Stammzellpathologie (Bubendorf)
UniBasel Contributors:Tamm, Michael and Bubendorf, Lukas and Brutsche, Martin and Pless, Miklos and Buess, Martin
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:American Thoracic Society
ISSN:0003-0805
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:21 Jun 2013 12:29
Deposited On:21 Jun 2013 12:24

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