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Lung cancer and COPD are two main smoke-related lung diseases. COPD patients have an increased risk to develop lung cancer - especially squamous cell carcinoma (SCC) - independent of their smoking history. The genetic background of this association has not been elucidated. We explored whether there are consistent gene expression changes in SCC and COPD that might explain their intricate association. To identify genes involved in the pathogenesis of SCC, we compared histological normal bronchial tissues of patients without COPD (GOLD stage 0, n=10) with SCC tumor tissue of patients without COPD (GOLD stage 0, n=17). To identify genes involved in the pathogenesis of COPD, we compared the same bronchial tissues of patients without COPD (GOLD stage 0, n=10) with patients with mild COPD (GOLD stage I or II, n=10) and severe COPD (GOLD stage IV, n=8). All patients had a similar smoking background and none of the patients used steroids or chemotherapy. We used laser microdissection microscopy to isolate only histological normal bronchial epithelial cells from the bronchial tissues and the transformed epithelial tumor cells from the SCC tissues. RNA was isolated and amplified for 1 round to yield sufficient RNA for hybridization on Agilent Whole Human Genome Arrays (44K). Expression data were analyzed using BRB-Array tools.

We identified 8169 significant genes using Significant Analysis of Microarrays (SAM) that were related to the pathogenesis of SCC. Using the same approach, no significant genes were identified related to the pathogenesis of COPD. This lack of significant genes in the pathogenesis of COPD is probably related to the similar cell morphology of the bronchial epithelium samples in patients with and without COPD. To allow identification of small differences in gene expression levels involved in the pathogenesis of COPD, we analyzed groups of genes that were combined based on similar gene ontology categories or involvement in the same pathways (Biocarta). Since we were interested in consistent gene expression changes in the pathogenesis of SCC and COPD, we analyzed the 8169 significant genes related to the pathogenesis of SCC to search for significant groups of genes involved in the pathogenesis of COPD.

Preliminary analysis showed 106 significant gene ontologies and 8 significant pathways related to the pathogenesis of COPD. Since we started our analysis with genes significantly deregulated in SCC, these genes are also related to the pathogenesis of SCC. The significant pathways included hypoxia/p53 related pathways and calpain-pathways involved in cell motility and cell spread and will be further elucidated for their biological relevance in relation to the overlap of pathogenesis of SCC and COPD. Although lung cancer and COPD are clinically two different diseases, an overlap in origin of both diseases seems reasonable.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA