Identification of key biomarkers and immune infiltration in Minimal Change Disease: Novel Insights from bioinformatics analysis

Abstract Background Minimal change disease (MCD) is not a simple immune disease, and its pathogenesis has not been elucidated because of its complexity in terms of the glomerular microenvironment and genetic susceptibility. Hence the therapeutic approach is equally imprecise. Methods We downloaded GSE108109 from the Gene Expression Omnibus (GEO) database for bioinformatic analyses. Genome-wide expression analysis (GSEA) and functional enrichment analysis of differentially expressed genes (DEGs) were performed. Single sample gene set enrichment analysis (ssGSEA) was applied to assess the level of immune infiltration patterns of diseases. Protein-Protein Interaction (PPI) network was constructed to identify hub genes. Hub genes were intersected with immune-related genes downloaded from the Immunology Database and Analysis Portal (ImmPort) to obtain key genes. In addition, the expression levels of key genes were validated in the Kidney Interactive Transcriptomics webpage and Nephroseq database. Receiver operating characteristic (ROC) analysis and principal component analysis (PCA) was performed to explore the value of key genes for MCD diagnosis. Results 1029 DEGs were screened, of which 493 were up-regulated, and 536 were down-regulated. GSEA analysis revealed that DEGs were significantly enriched in three pathways, including T-cell receptor signaling pathway, natural killer cell-mediated cytotoxicity, and B-cell receptor signaling pathway. In addition, 17 of the 21 immune cell types were significantly different in MCD compared to the normal group. A total of five key genes (ISG15, IRF1, OAS1, RSAD2, BST2) were shown to play essential roles in the immune response. Among them, IRF1, OAS1, RSAD2, and BST2 were highly expressed in podocytes. Conclusions In this study, bioinformatics analysis revealed new insights into MCD: (1) Immune cell infiltration analysis provided new evidence and clues to the molecular mechanisms of MCD. (2) Key genes such as ISG15, IRF1, OAS1, RSAD2 and BST2 may contribute to the immunopathological process of MCD development.