Identification of potential ferroptosis hub genes in acute-on-chronic liver failure based on bioinformatics analysis and experimental verification

Abstract

Abstract Background Ferroptosis has an important role in developing Acute-on-chronic Liver Failure (ACLF). The present project aimed to identify and validate the potential ferroptosis-related genes in ACLF by bioinformatics analysis and experimental verification. Materials and Methods GSE139602 was obtained from the GEO dataset and intersected with ferroptosis genes. Ferroptosis-related differentially expressed genes (DEGs) between the ACLF tissue and healthy group were analyzed using bioinformatics methods. Analysis of enrichment, protein-protein interactions, and hub genes were conducted. Finally, we performed real-time quantitative PCR(RT-qPCR) to validate the expression of the hub genes. Results A total of 35 ferroptosis-related DEGs were screened, which were involved in biosynthesis of amino acids, peroxisome, and fluid shear stress and atherosclerosis. PPI network analysis indicated five ferroptosis-related hub genes namely HRAS, TXNRD1, NQO1, PSAT1, and SQSTM1. The experimental validation indicates that the expression levels of HRAS, TXNRD1, NQO1, and SQSTM1 were lower, while PSAT1 was higher in ACLF rats than that of healthy group. Conclusions Our findings reveal that PSAT1, TXNRD1, HRAS, SQSTM1 and NQO1 may affect the development of ACLF by regulating ferroptotic events. These results provide a valid reference for potential mechanisms and identification in ACLF.