Identification of hub fatty acid metabolism-related genes and immune infiltration in IgA nephropathy

Abstract Aims: To identify the potential mechanism of fatty acid metabolism (FAM)-related genes in IgA nephropathy (IgAN) and to explore its immune cell infiltration feature. Methods: IgAN datasets and FAM-related genes were respectively downloaded from GEO and MSigDB database. Differential expression analysis and WGCNA were used to identify overlapping genes. GO and KEGG analysis were conducted to explore the differences between IgAN and control. Furthermore, we utilized LASSO logistic regression to select a FAM-related gene predictive model. ROC was utilized to assess the efficacy of prognostic model. Immune cells and immune-related functions were analysed using CIBERSORT tool. Finally, the screened key genes were confirmed in blood derived IgAN and control patient, as well as in human mesangial cells (HMCs) after Gd-IgA stimulation by Real-time PCR. Results: A total of 12 hub genes associated with FAM were obtained in IgAN. A 4 gene predictive model was conducted via LASSO regression analysis and the AUC values showed that the model had a relatively good diagnostic performance. The immune infiltration results revealed that several immune cells are significantly associated with IgAN. Real-time PCR assay further confirmed that the expression of hub genes were significantly lower in IgAN patients and Gd-IgA treated HMCsthan those in control. Conclusion: This study utilized bioinformatics tools to unveiled immune cell infiltration that occurred in IgAN and investigate the potential genetic link between FAM and IgAN. It may predict the risk of IgAN and improve the diagnosis and prognosis of this condition.