title: Association between P(16INK4a) promoter methylation and non-small cell lung cancer: a meta-analysis.
abstract: BACKGROUND
  Aberrant methylation of CpG islands acquired in tumor cells in promoter regions plays an important role in carcinogenesis. Accumulated evidence demonstrates P(16INK4a) gene promoter hypermethylation is involved in non-small cell lung carcinoma (NSCLC), indicating it may be a potential biomarker for this disease. The aim of this study is to evaluate the frequency of P(16INK4a) gene promoter methylation between cancer tissue and autologous controls by summarizing published studies.
  
  
  METHODS
  By searching Medline, EMBSE and CNKI databases, the open published studies about P(16INK4a) gene promoter methylation and NSCLC were identified using a systematic search strategy. The pooled odds of P(16INK4A) promoter methylation in lung cancer tissue versus autologous controls were calculated by meta-analysis method.
  
  
  RESULTS
  Thirty-four studies, including 2 652 NSCLC patients with 5 175 samples were included in this meta-analysis. Generally, the frequency of P(16INK4A) promoter methylation ranged from 17% to 80% (median 44%) in the lung cancer tissue and 0 to 80% (median 15%) in the autologous controls, which indicated the methylation frequency in cancer tissue was much higher than that in autologous samples. We also find a strong and significant correlation between tumor tissue and autologous controls of P(16INK4A) promoter methylation frequency across studies (Correlation coefficient 0.71, 95% CI:0.51-0.83, P<0.0001). And the pooled odds ratio of P(16INK4A) promoter methylation in cancer tissue was 3.45 (95% CI: 2.63-4.54) compared to controls under random-effect model.
  
  
  CONCLUSIONS
  Frequency of P(16INK4a) promoter methylation in cancer tissue was much higher than that in autologous controls, indicating promoter methylation plays an important role in carcinogenesis of the NSCLC. Strong and significant correlation between tumor tissue and autologous samples of P(16INK4A) promoter methylation demonstrated a promising biomarker for NSCLC.
authors.affiliation: Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, China.
authors.forename: Jundong
authors.initials: J
authors.lastname: Gu
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Wen
authors.forename: Siwei
authors.initials: S
authors.lastname: Zhu
authors.forename: Feng
authors.initials: F
authors.lastname: Hua
authors.forename: Hui
authors.initials: H
authors.lastname: Zhao
authors.forename: Hongrui
authors.initials: H
authors.lastname: Xu
authors.forename: Jiacong
authors.initials: J
authors.lastname: You
authors.forename: Linlin
authors.initials: L
authors.lastname: Sun
authors.forename: Weiqiang
authors.initials: W
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Zhou
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012044:Regression Analysis
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16