Background: IgA nephropathy (IgAN) has become the leading cause of end-stage renal disease in young adults. Nevertheless, the current diagnosis exclusively relies on invasive renal biopsy, and specific treatment is deficient. Thus, our study aims to identify potential crucial genes, thereby providing novel biomarkers for the diagnosis and therapy of IgAN.
Methods: Three microarray datasets were downloaded from GEO official website. Differentially expressed genes (DEGs) were identified by limma package. GO and KEGG analysis were conducted. Tissue/organ-specific DEGs were distinguished via BioGPS. GSEA was utilized to elucidate the predominant enrichment pathways. The PPI network of DEGs was established, and hub genes were mined through Cytoscape. The CTD database was employed to determine the association between hub genes and IgAN. Infiltrating immune cells and their relationship to hub genes were evaluated based on CIBERSORT. Furthermore, the diagnostic effectiveness of hub markers was subsequently predicted using the ROC curves. The CMap database was applied to investigate potential therapeutic drugs. The expression level and diagnostic accuracy of TYROBP was validated in the cell model of IgAN and different renal pathologies.
Results: A total of 113 DEGs were screened, which were mostly enriched in peptidase regulator activity, regulation of cytokine production, and collagen-containing extracellular matrix. Among these DEGs, 67 genes manifested pronounced tissue and organ specificity. GSEA analysis revealed that the most significant enriched gene sets were involved in proteasome pathway. Ten hub genes (KNG1, FN1, ALB, PLG, IGF1, EGF, HRG, TYROBP, CSF1R, and ITGB2) were recognized. CTD showed a close connection between ALB, IGF, FN1 and IgAN. Immune infiltration analysis elucidated that IGF1, EGF, HRG, FN1, ITGB2, and TYROBP were closely associated with infiltrating immune cells. ROC curves reflected that all hub genes, especially TYROBP, exhibited a good diagnostic value for IgAN. Verteporfin, moxonidine, and procaine were the most significant three therapeutic drugs. Further exploration proved that TYROBP was not only highly expressed in IgAN, but exhibited high specificity for the diagnosis of IgAN.
Conclusions: This study may offer novel insights into the mechanisms involved in IgAN occurrence and progression and the selection of diagnostic markers and therapeutic targets for IgAN.
Keywords: Bioinformatics analysis; Biomarkers; Diagnosis; Hub genes; IgA nephropathy; Therapeutics.
© 2023. The Author(s).