Epigenetic regulation plays an essential role in immunity and inflammation in endometriosis. In this study, we aimed to explore differences in m6A regulators between endometriosis patients and normal women and analyze the effect of m6A modification on immune and inflammatory microenvironment. The samples for analysis were downloaded from the Gene Expression Omnibus database, including ectopic endometrium (EC), eutopic endometrium (EU), and normal eutopic endometrium (NM) samples from non-endometriosis women. The validation process involved utilizing our previous RNA-sequencing data. Subsequently, a correlation analysis was performed to ascertain the relationship between m6A and the inflammatory microenvironment profile, encompassing infiltrating immunocytes, immune-inflammation reaction gene sets, and human leukocyte antigen genes. LASSO analyses were used to develop risk signature. The findings of this study indicate that the m6A regulators FTO were observed to be significantly up-regulated, while YTHDF2, CBLL1, and METTL3 were down-regulated in endometriosis tissues. The CIBERSORT analysis revealed that the local inflammatory microenvironment of ectopic lesions plays a crucial role in the development of endometriosis. Notably, M2 macrophages exhibited a significant difference between the EC and NM groups. Moreover, M2 macrophages demonstrated a positive correlation with FTO (0.39) and a negative correlation with CBLL1 (− 0.35). Furthermore, consistent clustering of EC and EU samples resulted in the identification of three distinct cell subtypes. Among different cell subtypes, significant differences were in immunoinfiltrating cells, plasma cells, naive CD4 T cells, memory activated CD4 T cells, gamma delta T cells, resting NK cells and activated NK cells but not in macrophages. Furthermore, the identification of various compounds capable of targeting these m6A genes was achieved. In conclusions, our integrated bioinformatics analysis results demonstrated that m6A-related genes METTL3, CBLL1 and YTHDF2 may be useful biomarkers for endometriosis in ectopic endometrium. The potential therapeutic approach of targeting m6A regulators holds promise for the treatment of endometriosis.

表观遗传调控在子宫内膜异位症的免疫和炎症中起着至关重要的作用。在本研究中，我们旨在探讨子宫内膜异位症患者与正常女性之间 m6A 调节因子的差异，并分析 m6A 修饰对免疫和炎症微环境的影响。分析样本从基因表达综合数据库下载，包括非子宫内膜异位症女性的异位子宫内膜 （EC） 、在位子宫内膜 （EU） 和正常在位子宫内膜 （NM） 样本。验证过程涉及利用我们之前的 RNA 测序数据。随后，进行了相关性分析以确定 m6A 与炎症微环境谱之间的关系，包括浸润免疫细胞、免疫炎症反应基因集和人类白细胞抗原基因。LASSO 分析用于开发风险特征。本研究结果表明，在子宫内膜异位症组织中观察到 m6A 调节因子 FTO 显著上调，而 YTHDF2 、 CBLL1 和 METTL3 下调。CIBERSORT 分析显示，异位病变的局部炎症微环境在子宫内膜异位症的发展中起着至关重要的作用。值得注意的是，M2 巨噬细胞在 EC 和 NM 组之间表现出显着差异。此外，M2 巨噬细胞与 FTO 呈正相关 （0.39），与 CBLL1 呈负相关 （- 0.35）。此外，EC 和 EU 样品的一致聚类导致鉴定了三种不同的细胞亚型。 在不同细胞亚型中，免疫浸润细胞、浆细胞、初始 CD4 T 细胞、记忆激活的 CD4 T 细胞、γ δ T 细胞、静息 NK 细胞和活化的 NK 细胞存在显著差异，而在巨噬细胞中则无显著差异。此外，还鉴定了能够靶向这些 m6A 基因的各种化合物。综上所述，我们的综合生物信息学分析结果表明，m6A 相关基因 METTL3 、 CBLL1 和 YTHDF2 可能是异位子宫内膜异位症的有用生物标志物。靶向 m6A 调节因子的潜在治疗方法有望治疗子宫内膜异位症。