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中华妇幼临床医学杂志(电子版) ›› 2020, Vol. 16 ›› Issue (05) : 551 -557. doi: 10.3877/cma.j.issn.1673-5250.2020.05.008

所属专题： 文献；

论著

基于GEO数据库的不明原因复发性自然流产患者子宫内膜差异基因筛选及其生物信息学分析
陈恒禧1, 成姝婷2, 肖丽1, 黄薇1,†()   
  1. 1. 四川大学华西第二医院妇产科、出生缺陷与相关妇儿疾病教育部重点实验，成都　610041
    2. 四川大学基础医学与法医学院，成都　610041
  • 收稿日期:2019-10-01 修回日期:2020-08-01 出版日期:2020-10-01
  • 通信作者: 黄薇

Screening and bioinformatics analysis of differentially expressed genes in unexplained recurrent spontaneous abortion based on the GEO database

Hengxi Chen1, Shuting Cheng2, Li Xiao1, Wei Huang1,†()   

  1. 1. Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
    2. West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu 610041, Sichuan Province, China
  • Received:2019-10-01 Revised:2020-08-01 Published:2020-10-01
  • Corresponding author: Wei Huang
  • Supported by:
    Key Research and Development Program of Science and Technology Department of Sichuan Province(2019YFS0421)
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引用本文：

陈恒禧, 成姝婷, 肖丽, 黄薇. 基于GEO数据库的不明原因复发性自然流产患者子宫内膜差异基因筛选及其生物信息学分析[J]. 中华妇幼临床医学杂志(电子版), 2020, 16(05): 551-557.

Hengxi Chen, Shuting Cheng, Li Xiao, Wei Huang. Screening and bioinformatics analysis of differentially expressed genes in unexplained recurrent spontaneous abortion based on the GEO database[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2020, 16(05): 551-557.

目的

探讨不明原因复发性自然流产(URSA)患者子宫内膜差异基因筛选及其相关信号通路及生物学过程。

方法

在基因表达总览(GEO)数据库中，以"recurrent spontaneous abortion""recurrent pregnancy loss""endometrium""homo sapiens"为关键词，检索URSA患者子宫内膜基因芯片数据集。利用R语言对URSA患者子宫内膜基因芯片数据进行分析，筛选差异基因，并对不同芯片数据集间差异基因取交集，获得共同差异基因。利用David数据库对共同差异基因的基因本体(GO)及京都基因与基因组百科全书(KEGG)信号通路进行富集分析。利用STRING数据库对这些基因数据集的差异基因编码蛋白的蛋白质与蛋白质相互作用(PPI)网络进行构建，并采用Cytoscape软件(v3.0)进行可视化。

结果

①本研究获得GSE26787和GSE65099共计2个URSA患者子宫内膜基因数据集，对这2个数据集差异基因取交集，最终获得23个共差异基因，其中上调基因为19个，分别为ADM2、SH3D21、FGFR4、SULT2B1、NRG2、SERPINA4、NLRP5、FAM124B、MCOLN3、SLC7A1、PPP1R1B、SQLE、SLC24A4、PLPPR5、EPHB3、SMIM24、ZNF589、SOX7、EDN3；下调基因为4个，分别为PRKCB、ANG、IRX5、ATG9B。②共同差异基因GO富集分析获得BP、CC和MF共计3个部分结果。共同差异基因在BP中，主要涉及细胞Ca2＋稳态、血管生成及细胞内信号传导；在CC中，主要涉及膜的整体组分；在MF中，主要涉及受体结合。③KEGG通路富集分析结果显示，共同差异基因富集于ErbB信号通路(P＝0.070，FDR＝55.245)。涉及该信号通路的共同差异基因为NRG2和PRKCB。

结论

基于GEO数据库，采用生物信息学的方法筛选到参与URSA发生、发展的部分差异基因，并为进一步研究提供数据支撑。

关键词: 子宫内膜, 基因表达, 流产, 自然, 流产, 习惯性, 生物学过程, 妇女
Objective

To screen the differentially expressed genes in endometrial of patients diagnosed with unexplained recurrent spontaneous abortion (URSA) and explore the related pathways and biological processes.

Methods

This study was searched using " recurrent sporadic abortion" , " recurrent probability loss" , " endometrium" and " homo sapiens" as the search key words. The R language was used to analyze the microarray data, screen the differential genes, and intersect the differential genes between the datasets to obtain co-differentially expressed genes. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways of co-differentially expressed genes were enriched using the David database. The protein-protein interaction (PPI) network of co-differentially expressed genes encoding proteins in the data set was constructed by using STRING database, and visualized by using Cytoscape software (v3.0).

Results

①Two data sets, GSE26787 and GSE65099, were obtained in this study. Then, the difference genes of the two data sets were intersected, and finally 23 co-differentially expressed genes were screened. Among these 23 co-differentially expressed genes, there were 19 up-regulated genes (ADM2, SH3D21, FGFR4, SULT2B1, NRG2, SERPINA4, NLRP5, FAM124B, MCOLN3, SLC7A1, PPP1R1B, SQLE, SLC24A4, PLPPR5, EPHB3, SMIM24, ZNF589, SOX7, EDN3) and 4 down-regulated genes (PRKCB, ANG, IRX5, ATG9B). ②The Go enrichment analysis of co-differentially expressed genes obtained 3 parts including BP, CC and MF. Co-differential expressed genes of BP were mainly related to cellular calcium ion homeostasis, angiogenesis, and intracellular signal transduction. CC mainly involved the whole composition of the membrane; MF mainly involved receptor binding. ③KEGG pathway enrichment analysis showed that co-differentially expressed genes were enriched in ErbB signaling pathway (P=0.070, FDR=55.245). Co-differentially expressed genes involved in ErbB signaling pathway were NRG2 and PRKCB.

Conclusions

Some differentially expressed genes can be effectively screened by bioinformatics analysis, and it can provide the basis for further research.

Key words: Endometrium, Gene expression, Abortion, habitual, Abortion, spontaneous, Biological processes, Women
图1 GSE26787数据集差异表达基因热图
图2 GSE65099数据集差异表达基因热图
表1 GO富集分析共同差异基因
类型 GO序号 注释 P值 FDR 基因
BP 0006874 细胞Ca2＋稳态 0.002 2.676 EDN3、SLC24A4、PRKCB
  0001525 血管生成 0.010 11.174 ANG、ADM2、EPHB3
  0035556 细胞内信号传导 0.039 37.232 PPP1R1B、NRG2、PRKCB
CC 0005887 膜的整体组分 0.019 15.398 FGFR4、SLC24A4、SLC7A1、PLPPR5、EPHB3
MF 0005102 受体结合 0.090 62.059 ANG、NRG2
图3 GSE26787和GSE65099数据集差异基因PPI网络图
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