Gene expression signature of cigarette smoking and its role in lung adenocarcinoma development and survival

Maria Teresa Landi, Tatiana Dracheva, Melissa Rotunno, Jonine D. Figueroa, Huaitian Liu, Abhijit Dasgupta, Felecia E. Mann, Junya Fukuoka, Megan Hames, Andrew W. Bergen, Sharon E. Murphy, Ping Yang, Angela C. Pesatori, Dario Consonni, Pier Alberto Bertazzi, Sholom Wacholder, Joanna H. Shih, Neil E. Caporaso, Jin Jen

Research output: Contribution to journalArticlepeer-review

446 Scopus citations


Background: Tobacco smoking is responsbile for over 90% of lung cancer cases, and yet the precise molecular alterations induced by smoking in lung that develop into cancer and impact survival have remained obscure. Methodology/Principal Findings: We performed gene expression analysis using HG-U133A affymetrix chips on 135 fresh frozen tissue samples of adenocarcinoma and paired noninvolved lung tissue from current, former and never smokers, with biochemically validated smoking information, ANOVA analysis adjusted for potential confounders, multiple testing procedure, Gene Set Enrichment Analysis, and GO-functional classification were conducted for gene selection. Results were confirmed in independent adenocarcinoma and non-tumor tissues from two studies. We identified a gene expression signature characteristic of smoking that includes cell cycly genes, particularly those involved in the mitotic spindle formation (e.g., NEK2, TTK, PRC1). Expression of these genes strongly differentiated both smokers in lung tumors and early stage tumor tissue from non-tumor tissue (p 1.5, for each comparison), consistent with an important role for this pathway in lung carcinogenesis induced by smoking. These changes persisted many years after smoking cessation NEK2 (p

Original languageEnglish (US)
Article numbere1651
JournalPLoS One
Issue number2
StatePublished - Feb 20 2008
Externally publishedYes

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)


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