title: A chronic obstructive pulmonary disease related signature in squamous cell lung cancer.
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.
authors.affiliation: Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Mirjam C
authors.initials: MC
authors.lastname: Boelens
authors.forename: Adam M
authors.initials: AM
authors.lastname: Gustafson
authors.forename: Dirkje S
authors.initials: DS
authors.lastname: Postma
authors.forename: Klaas
authors.initials: K
authors.lastname: Kok
authors.forename: Gerben
authors.initials: G
authors.lastname: van der Vries
authors.forename: Pieter
authors.initials: P
authors.lastname: van der Vlies
authors.forename: Avrum
authors.initials: A
authors.lastname: Spira
authors.forename: Marc E
authors.initials: ME
authors.lastname: Lenburg
authors.forename: Marie
authors.initials: M
authors.lastname: Geerlings
authors.forename: Hannie
authors.initials: H
authors.lastname: Sietsma
authors.forename: Wim
authors.initials: W
authors.lastname: Timens
authors.forename: Anke
authors.initials: A
authors.lastname: van den Berg
authors.forename: Harry J M
authors.initials: HJ
authors.lastname: Groen
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D002869:Chromosome Aberrations; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000209:etiology / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D008928:Mitochondria / Q000235:genetics; D009367:Neoplasm Staging; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology
chemical_list: D014408:Biomarkers, Tumor