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Discrimination of Human Lung Neoplasm from Normal Lung by Two Target Genes

Department of Cardiothoracic Surgery, Department of Pediatrics, and Children's Cancer Research Center, Martin Luther University Halle-Wittenberg, Halle; and Department of Pediatrics, Technical University of Munich, Munich, Germany

Correspondence and requests for reprints should be addressed to Hans-Stefan Hofmann, M.D., Department of Cardiothoracic Surgery, Martin Luther Universität Halle-Wittenberg, Ernst Grube Strasse 4, 06097 Halle, Germany. E-mail: stefan.hofmann{at}medizin.uni-halle.de

Simple tools for discrimination of lung tissues can be useful in a fast machine-aided diagnosis, for example, by tumor-specific microarrays. We demonstrate that an easy ratio technique, based on the expression levels of only two genes differentially expressed in lung tumor and normal lung samples, allows discrimination of normal and neoplastic lung with a sensitivity of 100% and specificity of 90.5%. DNA microarray analysis of 99 lung tumor samples and 15 normal lung tissues revealed that receptor for advanced glycation end products (RAGE) mRNA is reduced fourfold (p = 7.8 x 10^–11) and cyclin-B2 mRNA is upregulated twofold (p = 5.9 x 10^–18) in lung carcinoma compared with normal lung. The microarray-calculated expression ratio of RAGE to cyclin-B2 was used in polymerase chain reaction analysis of 84 independent blinded samples to discriminate tumor and corresponding normal lung tissues. In 94.7% of the samples this quotient correctly distinguished non–small cell lung cancer from normal lung tissue, suggesting the RAGE/cyclin-B2 quotient as a potential means for diagnosis of lung cancer.

Key Words: cyclin-B2 • lung cancer • lung metastases • receptor for advanced glycation end products • tissue discrimination

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