A chronic obstructive pulmonary disease related signature in squamous cell lung cancer.
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.
Boelens
Mirjam C
MC
Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Gustafson
Adam M
AM
Postma
Dirkje S
DS
Kok
Klaas
K
van der Vries
Gerben
G
van der Vlies
Pieter
P
Spira
Avrum
A
Lenburg
Marc E
ME
Geerlings
Marie
M
Sietsma
Hannie
H
Timens
Wim
W
van den Berg
Anke
A
Groen
Harry J M
HJ
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
D014408:Biomarkers, Tumor