反复着床失败子宫内膜组织差异表达基因的生物信息学分析

傅惠佳; 王孟皓; 刘西茹

doi:10.16016/j.1000-5404.201901067

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反复着床失败子宫内膜组织差异表达基因的生物信息学分析

基础医学 | 更新时间：2026-01-09

- 反复着床失败子宫内膜组织差异表达基因的生物信息学分析
- Bioinformatics analysis of differentially expressed genes in endometrium with recurrent implantation failure
- 第三军医大学学报 2019年41卷第13期页码：1246-1252
- 作者机构：
  
  1.400016 重庆，重庆医科大学附属第一医院生殖医学中心
  2.400010 重庆，重庆医科大学附属第二医院肝胆外科
- 作者简介：
  
  [刘西茹，E-mail:157856325@qq.comLIU Xiru, E-mail:157856325@qq.com
- 基金信息：
  
  国家自然科学基金应急管理项目(81741022);国家重点研发计划(2018YFC1004103)
- DOI：10.16016/j.1000-5404.201901067
  中图分类号： R318.04;R394.3;R711.6
- 收稿：2019-01-08，
  
  修回：2019-02-19，
  
  纸质出版：2019-07-15
- 稿件说明：
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傅惠佳, 王孟皓, 刘西茹. 反复着床失败子宫内膜组织差异表达基因的生物信息学分析[J]. 第三军医大学学报, 2019,41(13):1246-1252.

Huijia FU, Menghao WANG, Xiru LIU. Bioinformatics analysis of differentially expressed genes in endometrium with recurrent implantation failure[J]. Journal of Third Military Medical University, 2019, 41(13): 1246-1252.
傅惠佳, 王孟皓, 刘西茹. 反复着床失败子宫内膜组织差异表达基因的生物信息学分析[J]. 第三军医大学学报, 2019,41(13):1246-1252. DOI： 10.16016/j.1000-5404.201901067.

Huijia FU, Menghao WANG, Xiru LIU. Bioinformatics analysis of differentially expressed genes in endometrium with recurrent implantation failure[J]. Journal of Third Military Medical University, 2019, 41(13): 1246-1252. DOI： 10.16016/j.1000-5404.201901067.

摘要

目的

应用生物信息学方法分析体外受精(

in vitro

fertilization，IVF)后反复着床失败(recurrent implantation failure，RIF)的相关基因，以探讨反复着床失败的发病机制。

方法

从美国国立生物技术信息中心(National Center for Biotechnology Information

NCBI)公共数据平台(Gene Expression Omnibus，GEO)下载基因芯片数据集GSE111974，使用R语言筛选出反复着床失败和正常生育女性子宫内膜组织的差异表达基因(differentiallyexpressed genes

DEGs)。再利用生物信息学分析工具DAVID(The database forannotation，visualization and integrated discovery)对差异基因进行基因本体论(Gene Ontology，GO)功能富集分析和京都基因和基因组百科全书(Kyoto encyclopedia of genes and genomes，KEGG)通路分析，利用STRING(Search Tool for the Retrieval of Interacting Genes)在线数据库和Cytoscape软件进行蛋白互作网络分析。

结果

初筛出170个明显差异表达的基因，其中上调者127个，下调者43个。GO功能富集显示：这些DEGs主要富集于细胞膜、内质网等区域，主要参与氧化还原过程、细胞周期阻滞、脂质代谢过程等；主要与血红素结合、信号传递器活性、维甲酸结合、过氧化物酶活性等功能簇相关。KEGG分析显示其主要参与代谢途径信号通路、催产素信号通路、肿瘤坏死因子信号通路等。STRING在线数据库和Cytoscape软件分析发现PTGS2、TOP2A、ACTA2等为反复着床失败的关键基因。

结论

采用生物信息学方法筛选出RIF患者子宫内膜组织差异表达的关键基因有PTGS2、TOP2A、ACTA2等，可能在RIF的发病机制中起重要作用。

Abstract

Objective

To investigate the related genes in the endometrium with recurrent implantation failure (RIF) after

in vitro

fertilization (IVF) by bioinformatics analysis in order to illustrate the underlying pathogenesis of RIF.

Methods

The dataset GSE111974 was downloaded from Gene Expression Omnibus (GEO) in National Center for Biotechnology Information (NCBI). R/Bioconductor packages "marray" and "limma" were applied to this model to screen out the differentially expressed gene (DEGs) in the patients with RIF compared with normal fertile controls. Then

the database for annotation

visualization and integrated discovery (DAVID) was employed to make Gene Ontology (GO) analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis to analyze the protein-protein interaction network by the Search Tool for the Retrieval of Interacting Genes (STRING) online database and Cytoscape software.

Results

There were 170 DEGs turning out

of which 127 genes were up-regulated and 43 were down-regulated. GO analysis shows that the DEGs mainly concentrate in cell membrane

endoplasmic reticulum and other areas

which primarily participate in oxidation-reduction process

cell cycle arrest and lipid metabolic process

etc

. Their molecular functions are involved in heme binding

signal transducer activity

retinoic acid binding and peroxidase activity. KEGG pathway analysis showed that these genes are mainly involved in metabolic pathways

oxytocin signaling pathway

and TNF signaling pathway

etc

. STRING online database and Cytoscape software found out that DEGs PTGS2

TOP2A and ACTA2 were the hub genes of RIF.

Conclusion

The key genes PTGS2

TOP2A and ACTA2 and transcription factors CEBPB

CDX2 and ESR1 may play important role in the pathogenesis of RIF.

关键词

Keywords

references

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