Identification of genes down-regulated during lung cancer progression: A cDNA array study

Background: Lung cancer remains a major health challenge in the world. Survival for patients with stage I disease ranges between 40-70%. This suggests that a significant proportion of patients with stage I NSCLC may actually be under-staged. Methods: In order to identify genes relevant for lung cancer development, we carried out cDNA array experiments employing 64 consecutive patients ( 58 men and 6 women) with a median age of 58 years and stage 1 or stage 2 non-small-cell lung cancer ( NSCLC). Results: Basic cDNA array data identified 14 genes as differentially regulated in the two groups. Quantitative RT-PCR analysis confirmed an effective different transcriptional regulation of 8 out of 14 genes analyzed. The products of these genes belong to different functional protein types, such as extra-cellular matrix proteins and proteases ( Decorin and MMP11), genes involved in DNA repair (XRCC1), regulator of angiogenesis ( VEGF), cell cycle regulators ( Cyclin D1) and tumor-suppressor genes ( Semaphorin 3B, WNT-5A and retinoblastoma-related Rb2/p130). Some previously described differences in expression patterns were confirmed by our array data. In addition, we identified and validated for the first time the reduced expression level of some genes during lung cancer progression. Conclusion: Comparative hybridization by means of cDNA arrays assisted in identifying a series of novel progression-associated changes in gene expression, confirming, at the same time, a number of previously described results.