对先兆子痫进展的基因表达和 DNA 甲基化进行综合分析。

Comprehensive analysis of gene expression and DNA methylation for preeclampsia progression.

机构信息

Department of Obstetrics, Dongying People's Hospital, Dongying, Shandong, China.

出版信息

J Chin Med Assoc. 2021 Apr 1;84(4):410-417. doi: 10.1097/JCMA.0000000000000499.

DOI:10.1097/JCMA.0000000000000499

PMID:33595987

Abstract

BACKGROUND

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

METHODS

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.

RESULTS

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.

CONCLUSION

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

摘要

背景

本研究旨在鉴定新的子痫前期（PE）相关甲基化基因，揭示 PE 的分子机制。

方法

从基因表达综合数据库中获取所有 PE 和正常样本的基因表达和 DNA 甲基化数据集。我们首先鉴定了 PE 和正常样本之间的差异表达基因（DEGs）和差异甲基化基因（DMGs），然后进行了功能富集分析。还对 DEGs 和 DMGs 进行了综合分析，以鉴定有价值的 PE 相关生物标志物。使用 MassARRAY 进行了甲基化验证。

结果

整合了三个 DNA 甲基化和三个基因表达数据集。我们获得了 1754 个 DEGs 和 99 个 DMGs，PE 样本中的阈值为 p 值<0.05、|Δbeta|>0.1 和 p 值<0.05。DEGs 的功能分析获得了细胞黏附分子和白细胞穿越内皮迁移。此外，通过基因表达和 DNA 甲基化数据集的综合分析，鉴定了几个有价值的 PE 生物标志物，包括 OCA2、CDK2AP1 和 ADAM12。验证了四个甲基化位点（cg03449867、cg09084244、cg09247979 和 cg24194674），其中 cg03449867 和 cg09084244 被发现呈高甲基化状态，与 OCA2 和 CDK2AP1 相关的基因在 PE 中较正常样本下调。cg24194674 呈低甲基化状态，其相关基因 ADAM12 在 PE 中较正常样本上调。