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

doi:10.3877/cma.j.issn.1673-5250.2020.05.008

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Ca^2＋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

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Ca^2＋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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