title: The association of microRNA expression with prognosis and progression in early-stage, non-small cell lung adenocarcinoma: a retrospective analysis of three cohorts.
abstract: OBJECTIVE
  There is increasing evidence that altered microRNA expression is associated with tumor progression and survival in cancer patients. We tested if the expression of specific microRNAs was associated with prognosis and disease progression in early-stage lung adenocarcinoma.
  
  
  METHODS
  The expression of miR-21, miR-17, and miR-155 was measured by quantitative RT-PCR in tissues from 317 non-small cell lung cancer (NSCLC) patients that originated from Maryland, Norway, and Japan. Kaplan-Meier and Cox regression analysis evaluated associations of microRNA expression with cancer-specific mortality and disease-free survival.
  
  
  RESULTS
  Elevated miR-21 (HR 2.06, 1.13-3.75), miR-17 (HR 2.00, 1.10-3.61), and miR-155 (HR 2.37, 1.27-4.42) was associated with worse cancer-specific mortality in the Maryland cohort. These were evaluated in two additional cohorts and only miR-21 was associated with worse cancer-specific mortality in the Norwegian cohort (HR 2.78, 1.22-6.31) and worse relapse-free survival in the Japanese cohort (HR 2.82, 1.57-5.07). More advanced stage tumors expressed significantly higher levels of miR-21 compared with TNM stage I tumors. TNM stage I patients were evaluated separately and high levels of miR-21 was associated with worse cancer-specific mortality (HR 2.16, 1.11-4.21) and relapse-free survival (3.40, 1.57-7.36) independent of other clinical factors.
  
  
  CONCLUSIONS
  This is the first study to report that increased miR-21 expression is associated with disease progression and survival in stage I lung cancer. This suggests that expression of miR-21 may contribute to lung carcinogenesis and serve as a therapeutic target or early-stage prognostic biomarker for lung adenocarcinoma.
authors.affiliation: Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Motonobu
authors.initials: M
authors.lastname: Saito
authors.forename: Aaron J
authors.initials: AJ
authors.lastname: Schetter
authors.forename: Steen
authors.initials: S
authors.lastname: Mollerup
authors.forename: Takashi
authors.initials: T
authors.lastname: Kohno
authors.forename: Vidar
authors.initials: V
authors.lastname: Skaug
authors.forename: Elise D
authors.initials: ED
authors.lastname: Bowman
authors.forename: Ewy A
authors.initials: EA
authors.lastname: Mathé
authors.forename: Seiichi
authors.initials: S
authors.lastname: Takenoshita
authors.forename: Jun
authors.initials: J
authors.lastname: Yokota
authors.forename: Aage
authors.initials: A
authors.lastname: Haugen
authors.forename: Curtis C
authors.initials: CC
authors.lastname: Harris
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; C524942:MIRN155 microRNA, human; C524941:MIRN17 microRNA, human; C524940:MIRN21 microRNA, human; D035683:MicroRNAs