Abstract 112: Concurrent analysis between copy number variation and gene expression of non-smoking lung cancer females in Taiwan

Abstract

Abstract Although smoking has been proved to be an important factor for lung cancer, the etiology and molecular mechanisms of non-smoking female lung cancer remain unclear. We collected paired normal and tumor lung tissues from 44 female non-smoking lung cancer patients. Copy number variation and Gene expression profiles were analyzed by Affymetrix U133plus 2.0 expression arrays and Affymetrix SNP 6.0 single nucleotide polymorphism (SNP) arrays. The data from two platforms were integrated for concurrent analyses in order to elucidate the putative molecular mechanisms. We first identified the probes located at the same region of gene expression and copy number variation (CNV). Next, we calculated the Pearson correlation coefficient to assess the association between log intensity values of mRNA expression and the corresponding averaged intensity values of SNP probes in both tumor and normal tissues. Genes were then selected based on the following two criteria: (1) the difference in expression-SNP correlations between normal and tumor tissues > 0.7, and (2) the absolute expression-SNP correlation of either normal or tumor >0.3. The selected genes were further analyzed by Ingenuity Pathway Analysis (IPA) to explore the related pathways and networks. Results of IPA showed that mitochondrial dysfunction, IGF-1 signaling, and cell cycle: G1/S checkpoint regulation pathways were significantly dysregulated in tumor tissues. The associations between lung cancer and genomic alternations in these enriched pathways have been reported previously, such as overexpression of IGF1R in IGF-1 signaling pathway might resist EGFR inhibitors used in lung cancer treatment. In summary, with the integrated data of copy number variation and expression, the concurrent analyses help to dissect lung carcinogenesis of non-smoking lung cancer females in Taiwan. 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 112.