子宫内膜异位症不同分期患者内膜组织异常表达基因及相关细胞死亡方式分析

Analysis of abnormal expression genes and related cell death patterns in endometriosis patients with different stages

目的探讨子宫内膜异位症不同分期患者子宫内膜组织异常基因表达情况,并挖掘最相关细胞死亡途径。方法检索美国国立生物技术信息中心(NCBI)的GEO(Gene Expression Omnibus)数据库子宫内膜异位症患者子宫内膜组织表达谱芯片,通过GEO2R工具筛选差异基因,并利用DAVID数据库进行生物学过程通路富集分析,将差异基因与GeneCards检索得到的五种细胞死亡相关基因交集分析,以判别最高相关性的细胞死亡方式。结果最终纳入一项子宫内膜异位症患者子宫内膜组织表达谱芯片数据,共涉及111例子宫内膜组织样本。筛选出子宫内膜异位症疾病相关异常表达基因431个(|logFC|>2.5,调整后P值<0.05),在RNA聚合酶II启动子转录的正调控、细胞增殖、细胞分裂、凋亡过程正调控和细胞内信号转导等60条通路显著富集(P<0.05)。IFI6等14种基因在微轻度与中重度子宫内膜异位症患者内膜组织存在显著表达差异(调整后P值<0.05)。在五种细胞死亡方式中,凋亡与子宫内膜异位症患者子宫内膜组织细胞最为相关,共有1058个交集基因。结论子宫内膜异位症患者子宫内膜组织基因表达存在显著异常,与凋亡相关基因关联密切,不同分期的子宫内膜异位症患者也许能够通过子宫内膜组织基因表达差异进行区分。

Objective To investigate the abnormal gene expression in endometrial tissue of patients with different stages of endometriosis,and explore the most relevant cell death pathway.MethodsWe searched the GEO(Gene Expression Omnibus)database of National Center for Biotechnology Information(NCBI)for the expression profile chip of endometriosis.The differential genes were screened by GEO2R tool,and the biological process pathway enrichment was analyzed by David database.In order to identify the most relevant mode of cell death,we conducted the intersection analysis of differential genes and retrieved five cell death related genes from GeneCards.ResultsA total of 111 samples of endometrial tissue were included in the final analysis.432 abnormal expression genes(|logFC|>2.5,adjusted P<0.05)were screened.They were significantly enriched in 60 pathways including positive regulation of RNA polymerase II promoter transcription,cell proliferation,cell division,positive regulation of apoptosis and intracellular signal transduction(P<0.05).There were significant differences in the expression of 14 genes such as IFI6 between different stages of endometriosis(P<0.05).Among the five cell death patterns with 1058 overlapping genes,apoptosis was the most closely related to endometriosis.ConclusionThe gene expression in endometrium of patients with endometriosis is significantly abnormal,which is closely related to apoptosis.Patients with different stages of endometriosis may be distinguished by the difference of gene expression in endometrium.