title: The prognostic value of global DNA hypomethylation in cancer: a meta-analysis.
abstract: BACKGROUND
  Aberrant methylation of the global genome has been investigated as a prognostic indicator in various cancers, but the results are controversial and ambiguous.
  
  
  RESULTS
  This meta-analysis presents pooled estimates of the evidence to elucidate this issue. We searched the electronic databases: PubMed, Embase, ISI Web of Science and the Cochrane library (up to August 2013) to identify all of the relevant studies. The association between the level of surrogates' indexes of genome-wide hypomethylation (LINE-1, Alu and Sat-α) and the overall survival (OS) of cancer patients was examined. In addition, the pooled hazard ratios (HRs) with their 95% confidence interval (95%CI) were calculated to estimate the influences through fixed-effects and random-effects model. Finally, twenty studies with total population of 5447 met the inclusion criteria. The results indicate that the summary HRs for the studies employing LINE-1, Alu, and Sat-α repetitive elements also show that the global DNA hypomethylation have significant desirable effects on the tumour prognostic value. The pooled HRs (and CIs) of LINE-1, Alu and Sat-α were 1.83 (1.38-2.44), 2.00 (1.16-3.45), and 2.92 (1.04-8.25), with a heterogeneity measure index of I2 (and p-value) shows of 66.6% (p = 0.001), 57.1% (p = 0.053) and 68.2% (p = 0.076) respectively. The meta-regression and subgroup analysis indicated that the percentage of hypomethylated sample of cancer patients is one source of heterogeneity.
  
  
  CONCLUSIONS
  Our meta-analysis findings support the hypothesis that the global DNA hypomethylation is associated with a detrimental prognosis in tumour patients.
authors.affiliation: Department of Preventive Medicine, School of Public Health, Sun Yat-sen University, Guangzhou, P.R. China; Department of Toxicology, Guangzhou Center for Disease Control and Prevention, Guangzhou, P.R. China.
authors.forename: Jinhui
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Thoracic Oncology, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China.
authors.forename: Qingyuan
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Department of Epidemiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, P.R. China; Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Medical Statistics & Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, P.R. China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Zeng
authors.affiliation: Department of Toxicology, Guangzhou Center for Disease Control and Prevention, Guangzhou, P.R. China.
authors.forename: Wenxue
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Preventive Medicine, School of Public Health, Sun Yat-sen University, Guangzhou, P.R. China.
authors.forename: Zhini
authors.initials: Z
authors.lastname: He
authors.affiliation: Department of Preventive Medicine, School of Public Health, Sun Yat-sen University, Guangzhou, P.R. China.
authors.forename: Wen
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Toxicology, Guangzhou Center for Disease Control and Prevention, Guangzhou, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Department of Preventive Medicine, School of Public Health, Sun Yat-sen University, Guangzhou, P.R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
mesh_terms: D020087:Alu Elements / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism*; D004276:DNA, Satellite / Q000235:genetics; D044127:Epigenesis, Genetic; D015894:Genome, Human; D006801:Humans; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D004276:DNA, Satellite