Bioinformatic Analysis Combined With Experimental Validation Reveals Novel Hub Genes and Pathways Associated With Focal Segmental Glomerulosclerosis
Background: Focal segmental glomerulosclerosis (FSGS) is a type of nephrotic syndrome leading to end-stage renal disease, and this study aimed to explore the hub genes and pathways associated with FSGS to identify potential diagnostic and therapeutic targets.Methods: We downloaded the microarray dat...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-01-01
|
| Series: | Frontiers in Molecular Biosciences |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2021.691966/full |
| _version_ | 1798025709750321152 |
|---|---|
| author | Yan-Pei Hou Tian-Tian Diao Zhi-Hui Xu Xin-Yue Mao Xin-Yue Mao Chang Wang Chang Wang Bing Li Bing Li |
| author_facet | Yan-Pei Hou Tian-Tian Diao Zhi-Hui Xu Xin-Yue Mao Xin-Yue Mao Chang Wang Chang Wang Bing Li Bing Li |
| author_sort | Yan-Pei Hou |
| collection | DOAJ |
| description | Background: Focal segmental glomerulosclerosis (FSGS) is a type of nephrotic syndrome leading to end-stage renal disease, and this study aimed to explore the hub genes and pathways associated with FSGS to identify potential diagnostic and therapeutic targets.Methods: We downloaded the microarray datasets GSE121233 and GSE129973 from the Gene Expression Omnibus (GEO) database. The datasets comprise 25 FSGS samples and 25 normal samples. The differential expression genes (DEGs) were identified using the R package “limma”. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the database for Annotation, Visualization and Integrated Discovery (DAVID) to identify the pathways and functional annotation of the DEGs. The protein–protein interaction (PPI) was constructed based on the Search Tool for the Retrieval of Interacting Genes (STRING) database and visualized using Cytoscape software. The hub genes of the DEGs were then evaluated using the cytoHubba plugin of Cytoscape. The expression of the hub genes was validated by quantitative real-time polymerase chain reaction (qRT-PCR) using the FSGS rat model, and receiver operating characteristic (ROC) curve analysis was performed to validate the accuracy of these hub genes.Results: A total of 45 DEGs including 18 upregulated and 27 downregulated DEGs, were identified in the two GSE datasets (GSE121233 and GSE129973). Among them, five hub genes with a high degree of connectivity were selected. From the PPI network, of the top five hub genes, FN1 was upregulated, while ALB, EGF, TTR, and KNG1 were downregulated. The qRT-PCR analysis of FSGS rats confirmed that the expression of FN1 was upregulated and that of EGF and TTR was downregulated. The ROC analysis indicated that FN1, EGF, and TTR showed considerable diagnostic efficiency for FSGS.Conclusion: Three novel FSGS-specific genes were identified through bioinformatic analysis combined with experimental validation, which may promote our understanding of the molecular underpinning of FSGS and provide potential therapeutic targets for the clinical management. |
| first_indexed | 2024-04-11T18:23:13Z |
| format | Article |
| id | doaj.art-725df4ec927642409ccba4e9d4186dad |
| institution | Directory Open Access Journal |
| issn | 2296-889X |
| language | English |
| last_indexed | 2024-04-11T18:23:13Z |
| publishDate | 2022-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-725df4ec927642409ccba4e9d4186dad2022-12-22T04:09:42ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2022-01-01810.3389/fmolb.2021.691966691966Bioinformatic Analysis Combined With Experimental Validation Reveals Novel Hub Genes and Pathways Associated With Focal Segmental GlomerulosclerosisYan-Pei Hou0Tian-Tian Diao1Zhi-Hui Xu2Xin-Yue Mao3Xin-Yue Mao4Chang Wang5Chang Wang6Bing Li7Bing Li8Department of Nephrology, Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Pediatrics, First Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Nephrology, Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Nephrology, Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Nephrology, Second Affiliated Hospital of Hainan Medical University, Haikou, ChinaDepartment of Nephrology, Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Nephrology, Second Affiliated Hospital of Hainan Medical University, Haikou, ChinaDepartment of Nephrology, Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Nephrology, Second Affiliated Hospital of Hainan Medical University, Haikou, ChinaBackground: Focal segmental glomerulosclerosis (FSGS) is a type of nephrotic syndrome leading to end-stage renal disease, and this study aimed to explore the hub genes and pathways associated with FSGS to identify potential diagnostic and therapeutic targets.Methods: We downloaded the microarray datasets GSE121233 and GSE129973 from the Gene Expression Omnibus (GEO) database. The datasets comprise 25 FSGS samples and 25 normal samples. The differential expression genes (DEGs) were identified using the R package “limma”. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the database for Annotation, Visualization and Integrated Discovery (DAVID) to identify the pathways and functional annotation of the DEGs. The protein–protein interaction (PPI) was constructed based on the Search Tool for the Retrieval of Interacting Genes (STRING) database and visualized using Cytoscape software. The hub genes of the DEGs were then evaluated using the cytoHubba plugin of Cytoscape. The expression of the hub genes was validated by quantitative real-time polymerase chain reaction (qRT-PCR) using the FSGS rat model, and receiver operating characteristic (ROC) curve analysis was performed to validate the accuracy of these hub genes.Results: A total of 45 DEGs including 18 upregulated and 27 downregulated DEGs, were identified in the two GSE datasets (GSE121233 and GSE129973). Among them, five hub genes with a high degree of connectivity were selected. From the PPI network, of the top five hub genes, FN1 was upregulated, while ALB, EGF, TTR, and KNG1 were downregulated. The qRT-PCR analysis of FSGS rats confirmed that the expression of FN1 was upregulated and that of EGF and TTR was downregulated. The ROC analysis indicated that FN1, EGF, and TTR showed considerable diagnostic efficiency for FSGS.Conclusion: Three novel FSGS-specific genes were identified through bioinformatic analysis combined with experimental validation, which may promote our understanding of the molecular underpinning of FSGS and provide potential therapeutic targets for the clinical management.https://www.frontiersin.org/articles/10.3389/fmolb.2021.691966/fullbioinformatic analysisFSGSGEOhub genespathway |
| spellingShingle | Yan-Pei Hou Tian-Tian Diao Zhi-Hui Xu Xin-Yue Mao Xin-Yue Mao Chang Wang Chang Wang Bing Li Bing Li Bioinformatic Analysis Combined With Experimental Validation Reveals Novel Hub Genes and Pathways Associated With Focal Segmental Glomerulosclerosis Frontiers in Molecular Biosciences bioinformatic analysis FSGS GEO hub genes pathway |
| title | Bioinformatic Analysis Combined With Experimental Validation Reveals Novel Hub Genes and Pathways Associated With Focal Segmental Glomerulosclerosis |
| title_full | Bioinformatic Analysis Combined With Experimental Validation Reveals Novel Hub Genes and Pathways Associated With Focal Segmental Glomerulosclerosis |
| title_fullStr | Bioinformatic Analysis Combined With Experimental Validation Reveals Novel Hub Genes and Pathways Associated With Focal Segmental Glomerulosclerosis |
| title_full_unstemmed | Bioinformatic Analysis Combined With Experimental Validation Reveals Novel Hub Genes and Pathways Associated With Focal Segmental Glomerulosclerosis |
| title_short | Bioinformatic Analysis Combined With Experimental Validation Reveals Novel Hub Genes and Pathways Associated With Focal Segmental Glomerulosclerosis |
| title_sort | bioinformatic analysis combined with experimental validation reveals novel hub genes and pathways associated with focal segmental glomerulosclerosis |
| topic | bioinformatic analysis FSGS GEO hub genes pathway |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2021.691966/full |
| work_keys_str_mv | AT yanpeihou bioinformaticanalysiscombinedwithexperimentalvalidationrevealsnovelhubgenesandpathwaysassociatedwithfocalsegmentalglomerulosclerosis AT tiantiandiao bioinformaticanalysiscombinedwithexperimentalvalidationrevealsnovelhubgenesandpathwaysassociatedwithfocalsegmentalglomerulosclerosis AT zhihuixu bioinformaticanalysiscombinedwithexperimentalvalidationrevealsnovelhubgenesandpathwaysassociatedwithfocalsegmentalglomerulosclerosis AT xinyuemao bioinformaticanalysiscombinedwithexperimentalvalidationrevealsnovelhubgenesandpathwaysassociatedwithfocalsegmentalglomerulosclerosis AT xinyuemao bioinformaticanalysiscombinedwithexperimentalvalidationrevealsnovelhubgenesandpathwaysassociatedwithfocalsegmentalglomerulosclerosis AT changwang bioinformaticanalysiscombinedwithexperimentalvalidationrevealsnovelhubgenesandpathwaysassociatedwithfocalsegmentalglomerulosclerosis AT changwang bioinformaticanalysiscombinedwithexperimentalvalidationrevealsnovelhubgenesandpathwaysassociatedwithfocalsegmentalglomerulosclerosis AT bingli bioinformaticanalysiscombinedwithexperimentalvalidationrevealsnovelhubgenesandpathwaysassociatedwithfocalsegmentalglomerulosclerosis AT bingli bioinformaticanalysiscombinedwithexperimentalvalidationrevealsnovelhubgenesandpathwaysassociatedwithfocalsegmentalglomerulosclerosis |