Identification of ferroptosis-related genes in acute kidney injury by bioinformatic analysis

Abstract

ABSTRACT Background: Acute kidney injury (AKI) is a rapid decline in renal function characterized by a decrease in glomerular filtration rate in a short period. Ferroptosis affects the development of various kidney diseases. Therefore, searching for genes related to ferroptosis is crucial for understanding the occurrence and development of AKI. Methods: We obtained data from 18 samples (8 with acute kidney injury and 10 non-pathological tissue) in GSE53769 and 48 samples (39 with acute kidney injury and 9 non-pathological tissue) in GSE139061. We obtained differentially expressed genes (DEGs) of AKI/Control samples from both two datasets and intersected them with known ferroptosis-related genes (FRGs) to obtain ferroptosis-related DEGs (FRDEGs). GO annotation, KEGG pathway analysis, and GSEA analysis were conducted on the FRDEGs to understand their enriched biological functions and pathways. Next, we constructed the protein-protein interaction (PPI) network. Results: A total of 312 genes were obtained, which were abnormally expressed in both two datasets. After intersecting with known FRGs, 14 FRDEGs were obtained, namely ACSF2, ADIPOR1, ARF6, ATF3, ATF6, DPEP1, FH, GLRX5, MIOX, NAP1L1, NDRG1, PPARA, SPHK1, YY1AP1. The results of the immune infiltration analysis showed that multiple gene expressions among 14 genes are correlated with immune cell infiltration. Conclusion: Fourteen ferroptosis genes (ACSF2, ADIPOR1, ARF6, ATF3, ATF6, DPEP1, FH, GLRX5, MIOX, NAP1L1, NDRG1, PPARA, SPHK1, YY1AP1) are involved in the occurrence and development of AKI, among which NDRG1 might be the core functional gene, and PPARA is expected to become the most effective therapeutic target gene.