title: Reproducibility and concordance of differential DNA methylation and gene expression in cancer.
abstract: BACKGROUND
  Hundreds of genes with differential DNA methylation of promoters have been identified for various cancers. However, the reproducibility of differential DNA methylation discoveries for cancer and the relationship between DNA methylation and aberrant gene expression have not been systematically analysed.
  
  
  RESULTS
  Using array data for seven types of cancers, we first evaluated the effects of experimental batches on differential DNA methylation detection. Second, we compared the directions of DNA methylation changes detected from different datasets for the same cancer. Third, we evaluated the concordance between methylation and gene expression changes. Finally, we compared DNA methylation changes in different cancers. For a given cancer, the directions of methylation and expression changes detected from different datasets, excluding potential batch effects, were highly consistent. In different cancers, DNA hypermethylation was highly inversely correlated with the down-regulation of gene expression, whereas hypomethylation was only weakly correlated with the up-regulation of genes. Finally, we found that genes commonly hypomethylated in different cancers primarily performed functions associated with chronic inflammation, such as 'keratinization', 'chemotaxis' and 'immune response'.
  
  
  CONCLUSIONS
  Batch effects could greatly affect the discovery of DNA methylation biomarkers. For a particular cancer, both differential DNA methylation and gene expression can be reproducibly detected from different studies with no batch effects. While DNA hypermethylation is significantly linked to gene down-regulation, hypomethylation is only weakly correlated with gene up-regulation and is likely to be linked to chronic inflammation.
authors.affiliation: Bioinformatics Centre and Key Laboratory for NeuroInfomation of the Education Ministry of China, School of Life Science, University of Electronic Science and Technology of China, Chengdu, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Yao
authors.forename: Hongdong
authors.initials: H
authors.lastname: Li
authors.forename: Xiaopei
authors.initials: X
authors.lastname: Shen
authors.forename: Zheng
authors.initials: Z
authors.lastname: He
authors.forename: Lang
authors.initials: L
authors.lastname: He
authors.forename: Zheng
authors.initials: Z
authors.lastname: Guo
mesh_terms: D019295:Computational Biology / Q000379:methods*; D019175:DNA Methylation / Q000235:genetics*; D016208:Databases, Factual; D023281:Genomics; D006801:Humans; D009369:Neoplasms / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic / Q000235:genetics; D015203:Reproducibility of Results; D059467:Transcriptome / Q000235:genetics*