Comprehensive analysis of gene expression and DNA methylation for preeclampsia progression

The purpose of our study is to identify novel preeclampsia (PE)-related methylation genes and uncover the molecular mechanism of PE.

All the datasets of gene expression and DNA methylation datasets for PE and normal samples were obtained from the Gene Expression Omnibus database. We first identified the differentially expressed genes (DEGs) and differential methylation genes (DMGs) between PE and normal samples followed by the functional enrichment analysis. Comprehensive analysis of DEGs and DMGs was also conducted for the identification of valuable PE-related biomarkers. The methylation validation was also performed with MassARRAY.

Three DNA methylation and three gene expression datasets were incorporated. We obtained 1754 DEGs and 99 DMGs in PE samples with the thresholds of p value <0.05, |Δbeta| > 0.1, and p value <0.05, respectively. Functional analysis of DEGs obtained cell adhesion molecules and leukocyte transendothelial migration. Besides, several valuable biomarkers of PE, including OCA2, CDK2AP1, and ADAM12, were identified through the integrated analysis of gene expression and DNA methylation datasets. Four methylation sites (cg03449867, cg09084244, cg09247979, and cg24194674) were validated, among which cg03449867 and cg09084244 were found to be hypermethylated and the related genes of OCA2 and CDK2AP1 were downregulated in PE compared with normal samples simultaneously. cg24194674 was hypomethylated and its correlated gene ADAM12 was upregulated in PE compared with normal samples simultaneously.

Our study should be helpful for the development of potential biomarkers and therapeutic targets for PE.