title: Smoking status impacts microRNA mediated prognosis and lung adenocarcinoma biology.
abstract: BACKGROUND
  Cigarette smoke is associated with the majority of lung cancers: however, 25% of lung cancer patients are non-smokers, and half of all newly diagnosed lung cancer patients are former smokers. Lung tumors exhibit distinct epidemiological, clinical, pathological, and molecular features depending on smoking status, suggesting divergent mechanisms underlie tumorigenesis in smokers and non-smokers. MicroRNAs (miRNAs) are integral contributors to tumorigenesis and mediate biological responses to smoking. Based on the hypothesis that smoking-specific miRNA differences in lung adenocarcinomas reflect distinct tumorigenic processes selected by different smoking and non-smoking environments, we investigated the contribution of miRNA disruption to lung tumor biology and patient outcome in the context of smoking status.
  
  
  METHODS
  We applied a whole transcriptome sequencing based approach to interrogate miRNA levels in 94 patient-matched lung adenocarcinoma and non-malignant lung parenchymal tissue pairs from current, former and never smokers.
  
  
  RESULTS
  We discovered novel and distinct smoking status-specific patterns of miRNA and miRNA-mediated gene networks, and identified miRNAs that were prognostically significant in a smoking dependent manner.
  
  
  CONCLUSIONS
  We conclude that miRNAs disrupted in a smoking status-dependent manner affect distinct cellular pathways and differentially influence lung cancer patient prognosis in current, former and never smokers. Our findings may represent promising biologically relevant markers for lung cancer prognosis or therapeutic intervention.
authors.affiliation: Department of Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia V5Z 1L3, Canada. evucic@bccrc.ca.
authors.forename: Emily A
authors.initials: EA
authors.lastname: Vucic
authors.forename: Kelsie L
authors.initials: KL
authors.lastname: Thu
authors.forename: Larissa A
authors.initials: LA
authors.lastname: Pikor
authors.forename: Katey S S
authors.initials: KS
authors.lastname: Enfield
authors.forename: John
authors.initials: J
authors.lastname: Yee
authors.forename: John C
authors.initials: JC
authors.lastname: English
authors.forename: Calum E
authors.initials: CE
authors.lastname: MacAulay
authors.forename: Stephen
authors.initials: S
authors.lastname: Lam
authors.forename: Igor
authors.initials: I
authors.lastname: Jurisica
authors.forename: Wan L
authors.initials: WL
authors.lastname: Lam
mesh_terms: D000230:Adenocarcinoma / Q000209:etiology* / Q000401:mortality* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D016000:Cluster Analysis; D015331:Cohort Studies; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006801:Humans; D008175:Lung Neoplasms / Q000209:etiology* / Q000401:mortality* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009367:Neoplasm Staging; D063868:Patient Outcome Assessment; D011379:Prognosis; D034622:RNA Interference; D012907:Smoking
chemical_list: D035683:MicroRNAs