title: Role ofp14ARFandp15INK4Bpromoter methylation in patients with lung cancer: a systematic meta-analysis.
abstract: BACKGROUND
  The cyclin-dependent kinase inhibitorsp14ARFandp15INK4Bare tumor suppressor genes that have been reported to be silenced through promoter methylation in many human cancers. However, the strength of association betweenp14ARForp15INK4Bpromoter methylation and lung cancer remains unclear. Thus, we first determined whetherp14ARFandp15INK4Bpromoter methylation played a key role in the carcinogenesis of lung cancer.
  
  
  METHODS
  Eligible studies were selected from the online electronic databases. The pooled odds ratios or hazard ratios and 95% confidence intervals were calculated and summarized.
  
  
  RESULTS
  Finally, 12 studies with 625 lung cancer samples and 488 nontumor samples were included under the fixed-effects model. The pooled odds ratio showed thatp14ARFpromoter methylation was observed to be significantly higher in non-small-cell lung cancer (NSCLC) than in nontumor samples (P<0.001). No significant correlation was found betweenp15INK4Bpromoter methylation and lung cancer (P=0.27). Subgroup analysis of ethnicity revealed thatp14ARFpromoter methylation was significantly related to the risk of NSCLC in Asian and Caucasian populations. Subgroup analysis of sample type demonstrated thatp14ARFpromoter methylation was correlated with the risk of NSCLC in tissue samples (P<0.001), but not in bronchoalveolar lavage fluid and blood samples.P14ARFpromoter methylation from one study was not significantly correlated with overall survival of patients with NSCLC. Promoter methylation ofp14ARFandp15INK4Bwas not correlated with clinicopathological characteristics, such as gender status, smoking status, tumor differentiation, and tumor stage (P>0.05).
  
  
  CONCLUSIONS
  Our findings suggested thatp14ARFpromoter methylation may play an important role in the carcinogenesis of lung cancer, but notp15INK4Bpromoter methylation. Promoter methylation ofp14ARFandp15INK4Bwas not associated with clinicopathological parameters. However, more extensive large-scale studies are essential to further validate our study.
authors.affiliation: Department of Oncology, the First Affiliated Hospital of Jiaxing University, Jiaxing.
authors.forename: Xinmei
authors.initials: X
authors.lastname: Yang
authors.affiliation: Cancer Center, The First Hospital of Jilin University, Changchun.
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital, Zhejiang University, Zhejiang.
authors.forename: Wanrong
authors.initials: W
authors.lastname: Dai
authors.affiliation: Department of Thoracic Surgery, Hangzhou Red Cross Hospital, Hangzhou, People's Republic of China.
authors.forename: Bo
authors.initials: B
authors.lastname: Ye
keywords: lung cancer; methylation; overall survival; p14ARF; p15INK4B