Identification of ferroptosis-related genes in patients with renal ischemia-reperfusion injury

Abstract

Background Effective and curable treatment for kidney injury caused by renal ischemia/reperfusion (I/R) have been poor reported. Severe inflammation and ferroptosis resulting from the formation of reactive oxygen species (ROS)，is the main cause of kidney injury. Thus, identify the biomarkers associated with ferroptosis in renal ischemia-reperfusion injury (RIRI) is emergency and crucial. Methods Bioinformatics analysis was used to discover differentially expressed genes (DEGs) from the GSE43974 dataset. Differentially expressed ferroptosis-related genes were discovered as the intersection of DEGs and ferroptosis-related genes (DEFRGs). Using the "clusterProfiler" R package, gene ontology（GO）and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment studies were done on DEFRGs. The Cytoscape plugin Molecular Complex Detection (MCODE)was used to extract hub genes from a protein-protein interaction (PPI) network. Finally, regulatory networks for TF-hub genes and miRNA-hub genes were predicted and created using the miRNet software. Results There found a total of 3,950 DEGs between the RIRI and control samples. After taking the intersection of DEGs and ferroptosis-related genes, 74 DEFRGs are obtained. DEFRGs were enriched in reaction to oxidative stress, cellular response to chemical stress, response to nutritional levels, and cellular response to oxidative stress, according to the GO analysis. The KEGG enrichment analysis revealed that these DEFRGs were substantially related with the mitophagy-animal, kaposi sarcoma-associated herpesvirus infection, autophagy-animal, and IL17 signaling pathways. MCODE found ATF3, ATF4, ATG3, ATG5, BECN1, DDIT3, HSPA5, NFE2L2, WIPI1, and XBP1 as the hub genes. Finally，the receiver operating characteristic (ROC) analysis of the GSE43974 data set reveals ATF3, DDIT3, ATF4, and ATG3 with AUC greater than 0.70,which were identified as the biomarkers related RIRI. Conclusion ATF3, DDIT3, ATF4, and ATG3 were identified as ferroptosis-related hub genes and proven to have diagnostic value for RIRI.