A chronic obstructive pulmonary disease related signature in squamous cell lung cancer

• Published in: Lung cancer (Amsterdam, Netherlands) Vol. 72; no. 2; pp. 177 - 183
• Main Authors: Boelens, Mirjam C, Gustafson, Adam M, Postma, Dirkje S, Kok, Klaas, van der Vries, Gerben, van der Vlies, Pieter, Spira, Avrum, Lenburg, Marc E, Geerlings, Marie, Sietsma, Hannie, Timens, Wim, van den Berg, Anke, Groen, Harry J.M
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ireland Ltd 01-05-2011; Elsevier
• Subjects: Aged; Array-CGH; Biological and medical sciences; Biomarkers, Tumor - genetics; Carcinoma, Squamous Cell - etiology; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - pathology; Carcinoma, Squamous Cell - physiopathology; Chromosome Aberrations; Chromosomes, Human, Pair 5 - genetics; Chronic obstructive pulmonary disease, asthma; COPD; Dermatology; Down-Regulation - genetics; Expression array; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Hematology, Oncology and Palliative Medicine; Humans; Lung Neoplasms - etiology; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Lung Neoplasms - physiopathology; Male; Medical sciences; Microarray Analysis; Middle Aged; Mitochondria - genetics; Neoplasm Staging; Pneumology; Pulmonary Disease, Chronic Obstructive - complications; Pulmonary Disease, Chronic Obstructive - genetics; Pulmonary Disease, Chronic Obstructive - pathology; Pulmonary Disease, Chronic Obstructive - physiopathology; Pulmonary/Respiratory; Squamous cell lung carcinoma; Tumors; Tumors of the respiratory system and mediastinum; Tumors of the skin and soft tissue. Premalignant lesions; Array-CGH; Expression array; Squamous cell lung carcinoma; COPD; Lung disease; Skin disease; Squamous cell carcinoma; Basal cell carcinoma; Respiratory disease; Lung cancer; Lung; Malignant tumor; Gene expression; Array; Chronic; Cancerology; Bronchus disease; Chronic obstructive pulmonary disease; Obstructive pulmonary disease; Cell; Cancer; Pneumology
• ISSN: 0169-5002; 1872-8332
• DOI: 10.1016/j.lungcan.2010.08.014

Abstract The epidemiological relationship between squamous cell lung cancer (SCC) and chronic obstructive pulmonary disease (COPD), both smoking-related diseases, suggests that they have also a genetic basis. We compared 35 SCC patients with and without COPD with whole-genome gene expression profiles of laser microdissected tissue. Validation of differential expression was performed for 25 genes using quantitative (q)RT-PCR. Subsequently, we performed array-based CGH on the same tumor samples. We found that 374 probes were differentially expressed in SCC from patients with and without COPD. Forty-four probes were derived from genes with mitochondrial functions and 34 probes were located on 5q. All these probes showed a lower expression level in SCC from non-COPD patients. For a random selection of 25 mitochondrial and 5q genes, we confirmed the differential expression by qRT-PCR. Loss of 3p, 5q and 9p was observed, via array-CGH, to be more frequent in SCC from non-COPD patients as compared to SCC from COPD patients. Combination of chromosomal aberrations and the location of the differentially expressed genes showed significant association for loss of the 5q31.2–31.3 region and reduced expression of the 5q genes. In conclusion, a more frequent loss of 5q and a low expression of genes located on 5q in SCC tumors of non-COPD patients compared to tumors from COPD patients was identified suggesting that different oncogenetic pathways are operational in patients with and without COPD.