Tobacco smoke exposure-related pathway gene expression signature in the bronchial airway epithelium

Using primary human bronchial epithelial cells collected at bronchoscopy, we have perturbed signaling pathways important in regulation of response to tobacco smoke exposure and cancer development: ATM, BCL2, GPX1, NOS2, IKBKB, and SIRT1 Using gene expression profiles generated for each pathway and four independent gene expression datasets, we show that SIRT1 activity is significantly up-regulated in cytologically normal airway epithelial cells from active smokers compared to non-smokers; and in contrast, this activity is strikingly down-regulated in non-small cell lung cancer. 52 samples were run on Affymetrix Human Exon 1.0 ST microarrays (n=7 for ATM, n=8 for GPX1, n=7 for SIRT1, n=7 for NOS2, n=7 for IKBKB, n=8 for BCL2, and n=8 for GFP). The CEL files were processed using RMA and the ENTREZ Gene CDF file. 13 samples were removed either because of a low Pearson correlation between samples (n=1 SIRT1 sample) or a strong batch effect (n=2 ATM, n=2 BCL2, n=2 GFP, n=2 GPX1, n=1 IKBKB, n=2 NOS2, n=1 SIRT1 samples) as determined by PCA.