Integrated analysis of DNA methylation and transcriptome profiles to identify oxidative stress-related placenta-specific molecules for preeclampsia

Abstract

Background

Preeclampsia (PE) is a pregnancy-specific hypertensive disorder and one of the leading causes of maternal mortality. However, its etiology and pathogenesis are not yet fully clarified. This study aimed to uncover methylation-regulated oxidative stress-related placenta-specific molecules in PE.

Methods

Two PE datasets, GSE57767 and GSE25906, were subjected into this study. The oxidative stress-related genes were derived from GeneCards database. Differential methylation and expression analysis were applied to identify methylation-regulated oxidative stress-related genes in PE. The methylation-regulated oxidative stress-related placenta-specific molecules were determined by receiver operating characteristic (ROC) analysis. The single-gene gene set enrichment analysis (GSEA) were executed using the R “clusterProfiler.” The transcription factor (TF)-gene regulatory network of placenta-specific molecules was created through Network Analyst database and Cytoscape software. The drug-gene network of placenta-specific molecules were developed through DGIdb database and Cytoscape software. Eventually, we further examined biomarker expression trends in the collected clinical samples using real time quantitative PCR (RT-qPCR).

Results

A total of 13 methylation-regulated oxidative stress-related genes in PE were identified. Then, five genes (VIM, SNCA, PIK3CG, DNM2, and BMP6) were authenticated as methylation-regulated oxidative stress-related placenta-specific molecules in PE by ROC curves, suggesting a potential clinical diagnostic value. Single-gene GSEA pointed to the linkage of these five genes to the immune-related pathways, ferroptosis, and oxidative phosphorylation. Finally, a TF-gene regulatory network containing 32 nodes and 38 edges and a drug-gene network containing 126 nodes and 123 edges were generated based on methylation-regulated oxidative stress-related placenta-specific molecules in PE. Ultimately, the experimental results confirmed that the expression trends of VIM, PIK3CG, and BMP6 in our collected clinical samples were in line with the expression trends in the GSE25906 dataset.

Conclusion

Three genes, VIM, PIK3CG, and BMP6, were identified as methylation-regulated oxidative stress-related placenta-specific molecules in PE. This might have helped to understand the pathogenesis of the disease and might also have provided new perspectives on the diagnosis and treatment of PE.