Methylation associated pathway activity deregulation in lung adenocarcinoma

Abstract

Methylation impairments are tightly associated with gene expression and molecular pathway deregulation in cancer development. However, other regulatory mechanisms exist, making it important to distinguish those from methylation driven changes. Here we specifically assessed molecular pathway states associated with gene methylation in lung adenocarcinoma.

Paired gene expression and methylation data (id:GSE32867) were obtained from Gene Expression Omnibus. Self organizing maps (Wirth, H. et al.BMC Bioinformatics 2011;12:306 ) and in-house pathway signal flow algorithms were applied to describe expression (PSF) and methylation (mPSF) states in KEGG pathways.

35 and 24 KEGG pathways had at least one branch deregulated at significance levels p<0.05 and 0.05<p < 0.1, respectively. Because many pathways are multibranch, our analysis totalled in 54 up- (PSF>1) and 73 down-regulated (PSF<1) branches. From these branches, 19 were positively (mPSF<0) or negatively (mPSF>0) correlated with methylation states (see table).

In conclusion, only ∼15% of pathway deregulations were associated with changes in methylation state of genes, whereas the remainder should be attributed to other factors influencing gene expression, such as cancer-associated mutations, and alternative mechanisms of epigenetic control.