Relation between smoking history and gene expression profiles in lung adenocarcinomas

BMC Medical Genomics

Maria Planck⁵  Per Jönsson¹  Leif Johansson³  Sven-Börje Ewers⁵  Maria Soller⁶  Helen M Pettersson⁴  Annette Salomonsson⁵  Sofi Isaksson⁵  Anna Karlsson⁵  Mats Jönsson⁵  Göran Jönsson²  Johan Staaf² 

[1] Department of Thoracic Surgery, Clinical Sciences, Lund University and Skåne University Hospital, SE 22185, Lund, Sweden;CREATE Health Strategic Center for Translational Cancer Research, Lund University, BMC C13, SE 221 84, Lund, Sweden;Department of Pathology, Lund University and Regional Laboratories Region Skåne, SE 22185, Lund, Sweden;Center for Molecular Pathology, Department of Laboratory Medicine, Lund University, SE 20502, Malmö, Sweden;Department of Oncology, Clinical Sciences, Lund University and Skåne University Hospital, Barngatan 2:1, SE-22185, Lund, Sweden;Department of Clinical Genetics, Lund University and Regional Laboratories Region Skåne, SE 22185, Lund, Sweden

关键词: Immune response;    Never-smokers;    EGFR;    Adenocarcinoma;    Gene expression analysis;    Smoking;    Lung cancer;   

Others  :  1134909
DOI  :  10.1186/1755-8794-5-22

 received in 2011-11-29, accepted in 2012-06-07,  发布年份 2012

【 摘 要 】

Background

Lung cancer is the worldwide leading cause of death from cancer. Tobacco usage is the major pathogenic factor, but all lung cancers are not attributable to smoking. Specifically, lung cancer in never-smokers has been suggested to represent a distinct disease entity compared to lung cancer arising in smokers due to differences in etiology, natural history and response to specific treatment regimes. However, the genetic aberrations that differ between smokers and never-smokers’ lung carcinomas remain to a large extent unclear.

Methods

Unsupervised gene expression analysis of 39 primary lung adenocarcinomas was performed using Illumina HT-12 microarrays. Results from unsupervised analysis were validated in six external adenocarcinoma data sets (n=687), and six data sets comprising normal airway epithelial or normal lung tissue specimens (n=467). Supervised gene expression analysis between smokers and never-smokers were performed in seven adenocarcinoma data sets, and results validated in the six normal data sets.

Results

Initial unsupervised analysis of 39 adenocarcinomas identified two subgroups of which one harbored all never-smokers. A generated gene expression signature could subsequently identify never-smokers with 79-100% sensitivity in external adenocarcinoma data sets and with 76-88% sensitivity in the normal materials. A notable fraction of current/former smokers were grouped with never-smokers. Intriguingly, supervised analysis of never-smokers versus smokers in seven adenocarcinoma data sets generated similar results. Overlap in classification between the two approaches was high, indicating that both approaches identify a common set of samples from current/former smokers as potential never-smokers. The gene signature from unsupervised analysis included several genes implicated in lung tumorigenesis, immune-response associated pathways, genes previously associated with smoking, as well as marker genes for alveolar type II pneumocytes, while the best classifier from supervised analysis comprised genes strongly associated with proliferation, but also genes previously associated with smoking.

Conclusions

Based on gene expression profiling, we demonstrate that never-smokers can be identified with high sensitivity in both tumor material and normal airway epithelial specimens. Our results indicate that tumors arising in never-smokers, together with a subset of tumors from smokers, represent a distinct entity of lung adenocarcinomas. Taken together, these analyses provide further insight into the transcriptional patterns occurring in lung adenocarcinoma stratified by smoking history.

【 授权许可】

   
2012 Staaf et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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