| 引用本文： |
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雷蕾,叶庆华,李慧,等.子宫内膜异位症全基因组甲基化的研究[J].同济大学学报（医学版）,2016,37(6):41-46. [点击复制]
- LEI Lei,YE Qing-hua,LI Hui,et al.DNA methylome analysis with methylation microarray in patients with Endometriosis[J].同济大学学报（医学版）,2016,37(6):41-46. [点击复制]
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| 摘要: |
| 目的 子宫内膜异位症(endometriosis, EM)是妇科的多发病和常见病,发病率逐年增加。但内异症的发病机制至今并不明确。 EM类似恶性肿瘤的生物学行为可能是EM重要的发病机制之一,而恶性病变的发生、发展是以抑癌基因和癌基因遗传变异的积累为标志的,尤其是抑癌基因的异常甲基化。方法 抑癌基因非甲基化的CpG岛异常甲基化与人类恶性肿瘤的发生、转移密切相关。本实验采用成组病例对照方法,选取以手术病理确诊为卵巢型EM的汉族妇女6例为研究对象,选取患者的在位内膜组织标本和异位内膜组织标本各6例,选择同期住院患者中族别、年龄、文化程度等构成比相似的非EM的汉族妇女6例为对照组,选取患者的正常在位内膜组织标本6例。采用美国illumina公司生产的illumina Human Methylation450K Beadchip全基因组甲基化芯片进行全基因组甲基化研究,通过对全基因组甲基化芯片的总共48万个甲基化位点进行综合生物信息学分析。结果 通过对EM患者原位和异位内膜组织样品的全基因DNA甲基化修饰进行检测,并进行聚类分析、主成分分析、GO功能注释和KEGG信号通路分析,发现在EM患者的全基因甲基化修饰水平发生了显著变化。对差异甲基化的基因进行GO功能注释,结果发现富集的GO条目主要集中于免疫过程的抗原呈递和干扰素Y的相关通路,分子功能主要集中在协同转运、负离子跨膜转运等活性,而KEGG通路分析发现,1型糖尿病,自身免疫性甲状腺疾病相关信号通路被显著富集。其中,富集程度最高的通路是focal adhesion通路,参与其中的蛋白分子包括ECM-受体互作,细胞因子-受体互作,这些结果为揭示新的EM的发病分子机制提供了参考。结论 该实验为EM病因学研究提供新的理论依据,从而为EM分子生物学发病机制的研究提供新思路。 |
| 关键词: 子宫内膜 甲基化 GO分析 KEGG |
| DOI：10.16118/j.1008-0392.2016.06.008 |
| 投稿时间：2016-08-27 |
| 基金项目:上海浦东新区青年科技项目(PW2013B-4) |
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| DNA methylome analysis with methylation microarray in patients with Endometriosis |
| LEI Lei,YE Qing-hua,LI Hui,YANG Xin-hua |
| (Dept.of Obstetrics and Gynecology, East Hospital, Tongji University, Shanghai 200120, China;Dept.of Obstetrics and Gynecology, First Maternity and Child Health Care Hospital, Tongji University, Shanghai 200120, China) |
| Abstract: |
| Objective To analyze DNA methylome in endometriosis patients with methylation microarray. Methods Tissue specimens of eutopic endometrium and ectopic endometrium were taken from 6 patients with endometriosis(EM) and normal endometrial specimens taken from 6 non-EM women. The genome methylation was detected with metylation microarray(Illumina Human Methylation450K Beadchip) The methylome profiling data were analyzed by clustering and principal component analysis(PCA). GO and KEGG pathway analysis was performed on the differentially expressed genes for biological functions. Results Our results showed that various epigenetic aberrations existed in endometriosis. The aberrant methylation genes showed different signature in eutopic endometrium and ectopic endometrium of EM patients, and normal endometrim by PCA analysis. Furthermore, GO and KEGG analysis showed that these genes were enriched in antigen processing and presentation and interferon-gamma-mediated signaling pathway, and involvement in Type 1 diabetes mellitus, allograft rejection, graft-versus-host disease, and autoimmune thyroid disease. Conclusion Endometrial DNA methylation abnormity has been identified as one specific feature of endometriosis as compared with normal. DNA methylation genes may provide useful biomarker targets for diagnostic and prognostic purposes. |
| Key words: endometriosis methylome microarray GO analysis KEGG |
