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Published on: May 2, 2025
Identifying effective diagnostic biomarkers and immune infiltration features in chronic kidney disease by
Tao Liu1,2, Xing Xing Zhuang3, Xiu Juan Qin1
1Department of Pharmacy, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, China.
Insights
Researchers identified four key genes, including IL10RA, that are crucial in chronic kidney disease (CKD) development. These genes show potential as diagnostic markers and therapeutic targets for CKD, offering new hope for treatment.
Area of Science:
- Nephrology
- Immunology
- Bioinformatics
Background:
- Chronic kidney disease (CKD) involves inflammation and immune dysfunction, often progressing to end-stage kidney disease.
- Current diagnostic markers and therapeutic targets for CKD remain limited.
- Identifying novel biomarkers and therapeutic strategies is critical for managing CKD.
Purpose of the Study:
- To identify differentially expressed genes (DEGs) in CKD.
- To explore the functions of DEGs and identify hub genes.
- To evaluate the diagnostic significance and therapeutic potential of identified hub genes in CKD.
Main Methods:
- Data from GEO microarrays (GSE104948, GSE116626) were analyzed to find DEGs.
- Gene Ontology (GO), KEGG, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed.
- Weighted gene co-expression network analysis (WGCNA), protein-protein interaction networks, and ROC curve analysis were utilized.
Main Results:
- 657 DEGs were identified, highlighting roles in inflammation and immunomodulation in CKD.
- Four hub genes (IL10RA, CD45, CTSS, C1QA) were identified through WGCNA and network analysis.
- IL10RA showed the highest expression and significant correlation with immune cell infiltration and inflammatory pathways; potential drug targets were identified.
Conclusions:
- IL10RA and other identified hub molecules are implicated in CKD pathogenesis.
- These hub genes represent potential diagnostic biomarkers for CKD.
- IL10RA presents a promising target for novel therapeutic interventions in CKD treatment.
Abstract:
Background: Chronic kidney disease (CKD), characterized by sustained inflammation and immune dysfunction, is highly prevalent and can eventually progress to end-stage kidney disease. However, there is still a lack of effective and reliable diagnostic markers and therapeutic targets for CKD. Methods: First, we merged data from GEO microarrays (GSE104948 and GSE116626) to identify differentially expressed genes (DEGs) in CKD and healthy patient samples. Then, we conducted GO, KEGG, HPO, and WGCNA analyses to explore potential functions of DEGs and select clinically significant modules. Moreover, STRING was used to analyse protein-protein interactions. CytoHubba and MCODE algorithms in the cytoscape plug-in were performed to screen hub genes in the network. We then determined the diagnostic significance of the obtained hub genes by ROC and two validation datasets. Meanwhile, the expression level of the biomarkers was verified by IHC. Furthermore, we examined immunological cells' relationships with hub genes. Finally, GSEA was conducted to determine the biological functions that biomarkers are significantly enriched. STITCH and AutoDock Vina were used to predict and validate drug-gene interactions. Results: A total of 657 DEGs were screened and functional analysis emphasizes their important role in inflammatory responses and immunomodulation in CKD. Through WGCNA, the interaction network, ROC curves, and validation set, four hub genes (IL10RA, CD45, CTSS, and C1QA) were identified. Furthermore, IHC of CKD patients confirmed the results above. Immune infiltration analysis indicated that CKD had a significant increase in monocytes, M0 macrophages, and M1 macrophages but a decrease in regulatory T cells, activated dendritic cells, and so on. Moreover, four hub genes were statistically correlated with them. Further analysis exhibited that IL10RA, which obtained the highest expression level in hub genes, was involved in abnormalities in various immune cells and regulated a large number of immune system responses and inflammation-related pathways. In addition, the drug-gene interaction network contained four potential therapeutic drugs targeting IL10RA, and molecular docking might make this relationship viable. Conclusion: IL10RA and its related hub molecules might play a key role in the development of CKD and could be potential biomarkers in CKD.
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