Room 236, Building II, College of Science, CCU
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In vivo relationship between differential DNA methylation and differential gene expression in hepatocellular carcinoma
Tsunglin Liu (Institute of Bioinformatics and Biosignal Transduction, National Cheng Kung University)
Background
DNA methylation is involved in various key processes including carcinogenesis. Promoter methylation is known to cause gene silencing whereas gene-body methylation correlates positively with expression. Such position-dependent relationship is often obtained by comparing different genes in normal tissues. It is thus not clear whether the relationship holds for differential methylation and differential expression of the same genes across patients with hepatocellular carcinoma (HCC). A suitable statistical method that integrates methylation in multiple gene regions for explaining expression is also missing because methylation correlates with expression in a non-linear and composite manner.
Results
We probed global methylation at CpG islands in both promoter and gene-body regions for twelve liver tumor and the adjacent non-tumor tissues using a mDIP-Chip approach. Global expression levels were measured by microarray. Combining the two datasets, we found a position-dependent relationship between differential methylation and differential expression in HCC tissues, which resembles the previously discovered relationship between methylation and expression. We further proposed a piecewise-linear statistical model to identify genes whose differential expression could be explained by the combination of differential methylations in multiple gene regions. Via permutation and simulation analysis, we identified 122 significant genes and the false positive rate was estimated as ~34%.
Conclusion
Our data indicate that the position-dependent relationship between differential methylation and differential expression in HCC tissues is similar to the previous finding in normal tissues. The relationship was detected by our method with statistical significance, but the signal was moderate, suggesting a moderate impact of DNA methylation in HCC. For some of the identified genes, the aberrant expressions have been reported and our statistical models suggest that differential methylation in these genes is involved in regulating the expression.
