Renal tubular gene biomarkers identification based on immune infiltrates in focal segmental glomerulosclerosis
Objective The present study identified novel renal tubular biomarkers that may influence the diagnosis and treatment of focal segmental glomerulosclerosis (FSGS) based on immune infiltration.Methods Three FSGS microarray datasets, GSE108112, GSE133288 and GSE121211, were downloaded from the Gene Exp...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2022-12-01
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| Series: | Renal Failure |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/0886022X.2022.2081579 |
| _version_ | 1818488990681006080 |
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| author | JunYuan Bai XiaoWei Pu YunXia Zhang Enlai Dai |
| author_facet | JunYuan Bai XiaoWei Pu YunXia Zhang Enlai Dai |
| author_sort | JunYuan Bai |
| collection | DOAJ |
| description | Objective The present study identified novel renal tubular biomarkers that may influence the diagnosis and treatment of focal segmental glomerulosclerosis (FSGS) based on immune infiltration.Methods Three FSGS microarray datasets, GSE108112, GSE133288 and GSE121211, were downloaded from the Gene Expression Omnibus (GEO) database. The R statistical software limma package and the combat function of the sva package were applied for preprocessing and to remove the batch effects. Differentially expressed genes (DEGs) between 120 FSGS and 15 control samples were identified with the limma package. Disease Ontology (DO) pathway enrichment analysis was conducted with statistical R software to search for related diseases. Gene set enrichment analysis (GSEA) was used to interpret the gene expression data and it revealed many common biological pathways. A protein-protein interaction (PPI) network was built using the Search Tool for the Retrieval of Interacting Genes (STRING) database, and hub genes were identified by the Cytoscape (version 3.7.2) plug-in CytoHubba. The plug-in Molecular Complex Detection (MCODE) was used to screen hub modules of the PPI network in Cytoscape, while functional analysis of the hub genes and hub nodes involved in the submodule was performed by ClusterProfiler. The least absolute shrinkage and selection operator (LASSO) regression and support vector machine recursive feature elimination (SVM-RFE) analysis were used to screen characteristic genes and build a logistic regression model. Receiver operating characteristic (ROC) curve analyses were used to investigate the logistic regression model and it was then validated by an external dataset GSE125779, which contained 8 FSGS samples and 8 healthy subjects. Cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) was used to calculate the immune infiltration of FSGS samples.Results We acquired 179 DEGs, 79 genes with downregulated expression (44.1%) and 100 genes with upregulated expression (55.9%), in the FSGS samples. The DEGs were significantly associated with arteriosclerosis, kidney disease and arteriosclerotic cardiovascular disease. GSEA revealed that these gene sets were significantly enriched in allograft rejection signaling pathways and activation of immune response in biological processes. Fifteen genes were demonstrated to be hub genes by PPI, and three submodules were screened by MCODE linked with FSGS. Analysis by machine learning methodologies identified nuclear receptor subfamily 4 group A member 1 (NR4A1) and dual specificity phosphatase 1 (DUSP1) as sensitive tubular renal biomarkers in the diagnosis of FSGS, and they were selected as hub genes, as well as hub nodes which were enriched in the MAPK signaling pathway. Immune cell infiltration analysis revealed that the genetic biomarkers were both correlated with activated mast cells, which may amplify FSGS biological processes.Conclusion DUSP1 and NR4A1 were identified as sensitive potential biomarkers in the diagnosis of FSGS. Activated mast cells have a decisive effect on the occurrence and development of FSGS through tubular lesions and tubulointerstitial inflammation, and they are expected to become therapeutic targets in FSGS. |
| first_indexed | 2024-12-10T16:58:03Z |
| format | Article |
| id | doaj.art-7434e60f5e744f78a327878f8bba8d1e |
| institution | Directory Open Access Journal |
| issn | 0886-022X 1525-6049 |
| language | English |
| last_indexed | 2024-12-10T16:58:03Z |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Renal Failure |
| spelling | doaj.art-7434e60f5e744f78a327878f8bba8d1e2022-12-22T01:40:40ZengTaylor & Francis GroupRenal Failure0886-022X1525-60492022-12-0144196698610.1080/0886022X.2022.2081579Renal tubular gene biomarkers identification based on immune infiltrates in focal segmental glomerulosclerosisJunYuan Bai0XiaoWei Pu1YunXia Zhang2Enlai Dai3School of Traditional Chinese and Western Medicine, GanSu University of Chinese Medicine, GanSu, ChinaSchool of Traditional Chinese and Western Medicine, GanSu University of Chinese Medicine, GanSu, ChinaSchool of Traditional Chinese and Western Medicine, GanSu University of Chinese Medicine, GanSu, ChinaSchool of Traditional Chinese and Western Medicine, GanSu University of Chinese Medicine, GanSu, ChinaObjective The present study identified novel renal tubular biomarkers that may influence the diagnosis and treatment of focal segmental glomerulosclerosis (FSGS) based on immune infiltration.Methods Three FSGS microarray datasets, GSE108112, GSE133288 and GSE121211, were downloaded from the Gene Expression Omnibus (GEO) database. The R statistical software limma package and the combat function of the sva package were applied for preprocessing and to remove the batch effects. Differentially expressed genes (DEGs) between 120 FSGS and 15 control samples were identified with the limma package. Disease Ontology (DO) pathway enrichment analysis was conducted with statistical R software to search for related diseases. Gene set enrichment analysis (GSEA) was used to interpret the gene expression data and it revealed many common biological pathways. A protein-protein interaction (PPI) network was built using the Search Tool for the Retrieval of Interacting Genes (STRING) database, and hub genes were identified by the Cytoscape (version 3.7.2) plug-in CytoHubba. The plug-in Molecular Complex Detection (MCODE) was used to screen hub modules of the PPI network in Cytoscape, while functional analysis of the hub genes and hub nodes involved in the submodule was performed by ClusterProfiler. The least absolute shrinkage and selection operator (LASSO) regression and support vector machine recursive feature elimination (SVM-RFE) analysis were used to screen characteristic genes and build a logistic regression model. Receiver operating characteristic (ROC) curve analyses were used to investigate the logistic regression model and it was then validated by an external dataset GSE125779, which contained 8 FSGS samples and 8 healthy subjects. Cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) was used to calculate the immune infiltration of FSGS samples.Results We acquired 179 DEGs, 79 genes with downregulated expression (44.1%) and 100 genes with upregulated expression (55.9%), in the FSGS samples. The DEGs were significantly associated with arteriosclerosis, kidney disease and arteriosclerotic cardiovascular disease. GSEA revealed that these gene sets were significantly enriched in allograft rejection signaling pathways and activation of immune response in biological processes. Fifteen genes were demonstrated to be hub genes by PPI, and three submodules were screened by MCODE linked with FSGS. Analysis by machine learning methodologies identified nuclear receptor subfamily 4 group A member 1 (NR4A1) and dual specificity phosphatase 1 (DUSP1) as sensitive tubular renal biomarkers in the diagnosis of FSGS, and they were selected as hub genes, as well as hub nodes which were enriched in the MAPK signaling pathway. Immune cell infiltration analysis revealed that the genetic biomarkers were both correlated with activated mast cells, which may amplify FSGS biological processes.Conclusion DUSP1 and NR4A1 were identified as sensitive potential biomarkers in the diagnosis of FSGS. Activated mast cells have a decisive effect on the occurrence and development of FSGS through tubular lesions and tubulointerstitial inflammation, and they are expected to become therapeutic targets in FSGS.https://www.tandfonline.com/doi/10.1080/0886022X.2022.2081579Focal segmental glomerulosclerosistubularimmune infiltratesmachine learningnuclear receptor subfamily 4 group A member 1dual specificity phosphatase 1 |
| spellingShingle | JunYuan Bai XiaoWei Pu YunXia Zhang Enlai Dai Renal tubular gene biomarkers identification based on immune infiltrates in focal segmental glomerulosclerosis Renal Failure Focal segmental glomerulosclerosis tubular immune infiltrates machine learning nuclear receptor subfamily 4 group A member 1 dual specificity phosphatase 1 |
| title | Renal tubular gene biomarkers identification based on immune infiltrates in focal segmental glomerulosclerosis |
| title_full | Renal tubular gene biomarkers identification based on immune infiltrates in focal segmental glomerulosclerosis |
| title_fullStr | Renal tubular gene biomarkers identification based on immune infiltrates in focal segmental glomerulosclerosis |
| title_full_unstemmed | Renal tubular gene biomarkers identification based on immune infiltrates in focal segmental glomerulosclerosis |
| title_short | Renal tubular gene biomarkers identification based on immune infiltrates in focal segmental glomerulosclerosis |
| title_sort | renal tubular gene biomarkers identification based on immune infiltrates in focal segmental glomerulosclerosis |
| topic | Focal segmental glomerulosclerosis tubular immune infiltrates machine learning nuclear receptor subfamily 4 group A member 1 dual specificity phosphatase 1 |
| url | https://www.tandfonline.com/doi/10.1080/0886022X.2022.2081579 |
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