Screening of key genes and pathways involved in lupus nephritis based on GEO database

doi:10.3969/j.issn.1674-8115.2021.06.007

Abstract

Abstract: Objective

·To identify the differentially expressed genes and pathways involved in lupus nephritis (LN) using bioinformatics analysis.

Methods

·The matrix data of GSE32591 dataset was downloaded from the GEO database, and the limma package of R software was applied to standardize and screen the differentially expressed genes. The volcano map and heatmap of the differentially expressed genes were drawn by ggpubr and pheatmap packages. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of differentially expressed genes were performed using DAVID online database, and bar plot and bubble chart were drawn using R software ggplot package. STRING database and Cytoscape software were used to construct protein interaction networks of differentially expressed genes, and MCODE and cytohubba plug-ins were used to screen out the most significant modules and key genes involved in lupus nephritis. GSE99339 dataset was used to verify the differential expression of hub genes.

Results

·The GSE32591 data set was analyzed through the limma package, and 367 differentially expressed genes were obtained, including 253 up-regulated genes and 114 down-regulated genes. GO analysis and KEGG pathway enrichment analysis showed that differentially expressed genes were significantly enriched in virus defense response, cytoplasmic matrix, influenza A, tuberculosis, EB virus infection, complement pathway, etc. A protein interaction network of differentially expressed genes was constructed by STRING and Cytoscape, and 10 pivotal genes related to LN were identified. The hub genes are significantly differentially expressed in the GSE99339 validation dataset.

Conclusion

·The 367 differentially expressed genes and 10 hub genes are potential biomarkers of LN.

Key words: GEO database, lupus nephritis, systemic lupus erythematosus, bioinformatics, differentially expressed genes

CLC Number:

R593.24

Yin LIU, Tao YANG, Yu-sai XIE, Yu-zhu WANG. Screening of key genes and pathways involved in lupus nephritis based on GEO database[J]. JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE), 2021, 41(6): 749-755.

Figures/Tables 5

TrendMD

References 23

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No.	Gene symbol	Full name	Function
1	IFI6	Interferon α inducible protein 6	May play a critical role in cell apoptosis, negatively regulate intracellular apoptosis signaling pathways and TNFSF10-induced cell apoptosis
2	IFI27	Interferon α inducible protein 27	May play a role in type I interferon-induced apoptosis and TNFSF10-induced apoptosis, and has antiviral activity against hepatitis C virus (HCV) in the innate immune response
3	IFIT1	Interferon induced protein with tetratricopeptide repeats 1	Inhibits expression of viral messenger RNAs
4	IFIT2	Interferon induced protein with tetratricopeptide repeats 2	Inhibits expression of viral messenger RNAs and promotes apoptosis
5	IFIT3	Interferon induced protein with tetratricopeptide repeats 3	Inhibits cellular as well as viral processes, cell migration, proliferation, signaling, and viral. Negatively regulates the apoptotic effects of IFIT2
6	IFITM3	Interferon induced transmembrane protein 3	Interferon-induced antiviral protein inhibits virus from entering the cytoplasm of host cells
7	ISG15	ISG15 ubiquitin-like modifier	Mediates innate immune response to viral and mycobacterial infections
8	ISG20	Interferon stimulated exonuclease gene 20	Interferon-induced antiviral exo-ribonuclease acts on single-stranded RNA and has antiviral activity against RNA viruses such as HCV
9	MX1	MX dynamin like GTPase 1	Interferon-induced dynamin-like GTPase with antiviral activity against a wide range of RNA viruses and some DNA viruses
10	SAMHD1	SAM and HD domain containing deoxynucleoside triphosphate triphosphohydrolase 1	May play a role in the regulation of innate immune response

No.	Gene symbol	Full name	Function
1	IFI6	Interferon α inducible protein 6	May play a critical role in cell apoptosis, negatively regulate intracellular apoptosis signaling pathways and TNFSF10-induced cell apoptosis
2	IFI27	Interferon α inducible protein 27	May play a role in type I interferon-induced apoptosis and TNFSF10-induced apoptosis, and has antiviral activity against hepatitis C virus (HCV) in the innate immune response
3	IFIT1	Interferon induced protein with tetratricopeptide repeats 1	Inhibits expression of viral messenger RNAs
4	IFIT2	Interferon induced protein with tetratricopeptide repeats 2	Inhibits expression of viral messenger RNAs and promotes apoptosis
5	IFIT3	Interferon induced protein with tetratricopeptide repeats 3	Inhibits cellular as well as viral processes, cell migration, proliferation, signaling, and viral. Negatively regulates the apoptotic effects of IFIT2
6	IFITM3	Interferon induced transmembrane protein 3	Interferon-induced antiviral protein inhibits virus from entering the cytoplasm of host cells
7	ISG15	ISG15 ubiquitin-like modifier	Mediates innate immune response to viral and mycobacterial infections
8	ISG20	Interferon stimulated exonuclease gene 20	Interferon-induced antiviral exo-ribonuclease acts on single-stranded RNA and has antiviral activity against RNA viruses such as HCV
9	MX1	MX dynamin like GTPase 1	Interferon-induced dynamin-like GTPase with antiviral activity against a wide range of RNA viruses and some DNA viruses
10	SAMHD1	SAM and HD domain containing deoxynucleoside triphosphate triphosphohydrolase 1	May play a role in the regulation of innate immune response

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