Department of Gynecology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
Department of Dermatology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
Front Endocrinol (Lausanne). 2023 Mar 23;14:1093683. doi: 10.3389/fendo.2023.1093683. eCollection 2023.
The incidence of endometriosis (EMs), a common disease in gynecology, has increased over the years. Women suffer from the symptoms caused by EMs, such as chronic pelvic pain, dysmenorrhea, and infertility. However, the etiology and pathophysiology of EMs remain unclear. This study aimed to identify candidate genes of endometriosis through integrated analysis of genome-wide gene expression and DNA methylation profiles.
Eutopic and ectopic endometrial tissues were collected from patients who were diagnosed as ovarian EMs. Genome-wide methylation profiling identified 17551 differentially methylated loci, with 9777 hypermethylated and 7774 hypomethylated loci. Differentially methylated loci were mainly concentrated in the gene body and intergenic regions. Genome-wide gene expression profiling identified 1837 differentially expressed genes (DEGs), with 1079 genes upregulated and 758 downregulated in ectopic groups. Integrated analysis revealed that DNA methylation was negatively correlated to gene expression in most genomic regions, such as exon, 3'UTR, 5'UTR, and promoter. We also identified promoter-related (53 downregulated and 113 upregulated) and enhancer-related DMGs (212 downregulated and 232 upregulated), which were significantly correlated to the gene expression. Further validation of the top-ranked genes belonging to differentially methylated genes (DMGs) and DEGs revealed that , , , , , , , and were significant candidate genes in ovarian endometriosis.
Our study revealed the significance of DNA methylation in the gene expression in ovary endometriosis, which provides new insights and a molecular foundation for understanding the underlying mechanisms of endometriosis.
子宫内膜异位症（EMs）是妇科的常见病，近年来其发病率有所上升。女性患有 EMs 引起的症状，如慢性盆腔疼痛、痛经和不孕。然而，EMs 的病因和病理生理学仍不清楚。本研究旨在通过全基因组基因表达和 DNA 甲基化谱的综合分析，鉴定子宫内膜异位症的候选基因。
从被诊断为卵巢 EMs 的患者中收集了在位和异位子宫内膜组织。全基因组甲基化谱分析鉴定出 17551 个差异甲基化位点，其中 9777 个为高甲基化，7774 个为低甲基化。差异甲基化位点主要集中在基因体和基因间区。全基因组基因表达谱分析鉴定出 1837 个差异表达基因（DEGs），其中异位组中 1079 个基因上调，758 个基因下调。整合分析显示，在大多数基因组区域（如外显子、3'UTR、5'UTR 和启动子）中，DNA 甲基化与基因表达呈负相关。我们还鉴定了与基因表达显著相关的启动子相关（53 个下调和 113 个上调）和增强子相关 DMGs（212 个下调和 232 个上调）。对属于差异甲基化基因（DMGs）和差异表达基因（DEGs）的排名靠前的基因进行进一步验证，发现 、 、 、 、 、 、 和 是卵巢子宫内膜异位症的重要候选基因。
本研究揭示了 DNA 甲基化在卵巢子宫内膜异位症中基因表达的重要性，为理解子宫内膜异位症的潜在机制提供了新的见解和分子基础。
