Abstract A10: Gene expression analysis of malignancy associated changes in normal bronchial epithelium

Abstract

Abstract A10 Background Lung cancer is the number one cancer-related cause of death in the world. The poor prognosis for lung cancer patients is largely due to the lack of an effective non-invasive method to detect the disease in its early stage. Using quantitative nuclear morphometry of sputum cells, we have previously demonstrated that in the presence of tumour, cytologically normal appearing diploid cells may exhibit malignancy-associated changes (MACs) and that these changes may be used as surrogate markers for early detection. The molecular basis for MACs is not known. Objective Our objective is to identify malignancy-associated gene expression changes in normal bronchial epithelial cells obtained by bronchial brushing. Methods We compared the pre- and post-surgical resection gene expression profiles of bronchial epithelial cells obtained by brushing of airways in the lung opposite to the one containing the lung cancer. Agilent whole genome expression arrays were used to generate mRNA transcript profiles for seven paired normal bronchial brushings taken before and 3 to 6 months after surgical resection of the tumour. Ingenuity Pathway Analysis software was used to identify downstream expression targets of the soluble signaling factors VEGF, TGF-β, TNF-α, and IL-8, which have been reported to be secreted by lung tumour cells. The target genes identified were analyzed for malignancy induced differential gene expression between normal bronchial epithelial cells from cancerous and non-cancerous environments. Results We detected differential expression of multiple target genes in the bronchial brush cells. Genes that were found to be differentially expressed included downstream targets of the signaling molecules EGF,TGF-β, and VEGF. Conclusion Soluble signaling molecules secreted by lung malignancies induce MACs, as evident by altered gene expression after removal of the tumour. Although further investigation is necessary, our results are consistent with previous observation that lung tumours can induce MACs in normal appearing bronchial cells in the vicinity of the tumor. MACs may be a potential marker for early detection of lung cancer. This data also provides evidence that MACs can be measured quantitatively in bronchial brush cells using gene expression analysis. Citation Information: Cancer Prev Res 2008;1(7 Suppl):A10.