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A Training-Testing Approach to the Molecular Classification of Resected Non-Small Cell Lung Cancer

Vanderbilt-Ingram Cancer Center and Department of Medicine [N. Y., K. Y., T. P. D., S. N., D. P. C.], Department of Preventive Medicine [P. L., Y. S.], Department of Pathology [M. E., A. G., R. J.], Department of Cardiac and Thoracic Surgery [J. R. R.], and Department of Molecular Physiology and Biophysics [S. L., J. H. M.], Vanderbilt University School of Medicine, Nashville, Tennessee 37232-6838; Cardiovascular Surgical Associates, Saint Thomas Hospital, Nashville, Tennessee 37205 [J. C. N.]; and Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, Texas 75235 [J. D. M.]

ABSTRACT

Purpose:RNA expression patterns associated with non-small cell lung cancer subclassification have been reported, but there are substantial differences in the key genes and clinical features of these subsets casting doubt on their biological significance.

Experimental Design: In this study, we used a training-testing approach to test the reliability of cDNA microarray-based classifications of resected human non-small cell lung cancers (NSCLCs) analyzed by cDNA microarray.

Results: Groups of genes were identified that were able to differentiate primary tumors from normal lung and lung metastases, as well as identify known histological subgroups of NSCLCs. Groups of genes were identified to discriminate sample clusters. A blinded confirmatory set of tumors was correctly classified by using these patterns. Some histologically diagnosed large cell tumors were clearly classified by expression profile analysis as being either adenocarcinoma or squamous cell carcinoma, indicating that this group of tumors may not be genetically homogeneous. High -actinin-4 expression was identified as highly correlated with poor prognosis.

Conclusions: These results demonstrate that gene expression profiling can identify molecular classes of resected NSCLCs that correctly classifies a blinded test cohort, and correlates with and supplements standard histological evaluation.

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