Classification Of Lung Carcinoma Cell Lines By Integrated Information Of Epidermal Growth Factor Receptor And Met Abnormalities And Gene Expression Pattern Correlates With Response To Chemotherapy And Molecular Targeted Therapy

Purpose: We have previously reported that lung adenocarcinoma cell lines could be classified into two groups based on the integrated information of epidermal growth factor receptor and MET abnormalities and gene expression pattern (2009 AACR annual meeting). In this study we sought to validate this classification by analyzing gene expression data set of primary lung adenocarcinomas. Also, we investigated whether this classification is clinically relevant to therapeutic outcomes. Experimental Design: A panel of 40 lung carcinoma cell lines was analyzed. The activation levels of EGFR and MET were determined by Western blotting and gene expression data was obtained by Affymetrix Microarray. We retrieved gene expression data of 442 lung adenocarcinomas (Nature medicine, 2008, http://www.nature.com/nm/journal/v14/n8/abs/nm.1790.html?lang=en) and used them to validate our classification. Results: Forty lung carcinoma cell lines could be classified into two distinctive groups. Group I (n=26) was characterized by high levels of TTF-1, MUC1, CK7, MET, HER3, E-cadherin, Cox-2, and lamininC2. In contrast, Group II (n=14) showed high levels of vimentin, FGFR1, and TCF8. Group I was characterized by high phosphorylation levels of MET and EGFR, and frequent mutation and amplification of EGFR and MET. In contrast, Group II exhibited low activation levels of EGFR and MET, and no mutation or amplification of EGFR and MET. We validated this classification by analyzing gene expression data of 442 lung adenocarcinomas. By hierarchical clustering we identified two clusters (Cluster A and B) that corresponded to Group I and II, respectively. Cluster A and B were similar in prognosis but among patients who received adjuvant chemo- or radiotherapy, Cluster B showed better survival than Cluster A. This finding was corroborated by analyzing in vitro sensitivities to chemotherapeutic and molecular-targeted agents: Group II cell lines showed a tendency to be sensitive to paclitaxel and cisplatin while they showed resistance to EGFR inhibitor gefitinib. Conclusions: Lung adenocarcinoma cell lines can be classified into two groups with distinct gene expression patterns, genetic abnormalities and activation status of EGFR and MET. This classification will be clinically relevant with regard to clinical response to chemotherapy and molecular targeted therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1185.