cDNA array is a powerful method that allows for rapid analysis of many genes differentially expressed in a variety of tissues of interest. Using Affymetrix oligo-nucleotide based cDNA arrays, we have so far surveyed 65 primary tissues and examined gene expression differences between the tumor and normal lung tissues. Among the molecular pathways affected in lung cancers, we observed a consistent down regulation of genes involved in the TGF-beta signaling. We further observed that the loss of SMAD6 and SMAD7 appeared to be correlated with an improved tumor-related survival in NSCLC patients. In vitro experiments using siRNA technology are currently underway to examine the mechanism of SMAD6 inactivation in lung tumors. We are also using well established assays of TGF-beta functions to examine their functional differences between the lung tumor and normal cells.