Abstract 2944: Genome-wide transcriptional modulation screening in non-smoking female lung cancer in Taiwan

Lung cancer has become the leading cause of cancer death in Taiwan and in most countries. Although smoking has been the major risk factor for lung cancer, less than 20% smokers develop lung cancer. In Taiwan, only about 50% of lung cancer cases were related to smoking, while more than 90% lung cancer females were non-smokers. In this study, we collected gene expression microarrays to investigate the pathogenesis process. One hundred and twenty lung tumor samples and their normal counterparts from non-smoking females were collected from National Taiwan University Hospital and Taichung Veterans General Hospital. RNAs from 60 paired samples were examined using Affymetrix Human U133 plus2.0 microarray. Paired t-tests were used to identify differentially expressed genes between tumor and normal tissues. The preliminary results showed there were 791 differentially expressed genes (p-value −14 ). Ingenuity Pathway Analysis (IPA) was utilized for further functional and pathway analyses on these genes, and the axon guidance signaling pathway was the most significantly enriched pathway. Among genes in the axon guidance signaling pathway, SEMA5A was chosen for further investigation because it was the most significant down-regulated gene in tumor tissue. Its down-regulation was validated by both real-time PCR and immunohistochemistry (IHC). Furthermore, Kaplan-Meier survival analysis showed that patients with low SEMA5A expression had poor overall survival as compared to those who had high SEMA5A expression. This significant association was also observed in two published studies. Therefore, these results indicated that the SEMA5A may play an important role in the carcinogenesis and can be a potential prognosis biomarker for 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 2944.