Identification of genes associated with liver ischemia-reperfusion injury after liver transplantation by WGCNA and PPI network analyses

Liver transplantation is the only effective treatment for end-stage liver disease. The success of transplantation largely relies on liver ischemia/reperfusion injury (LIRI). However, the pathogenesis of LIRI remains unclear. In this study, we used the public dataset GSE12720, which contains liver transplants from both living and deceased donors, to identify differentially expressed genes (DEGs) before and after reperfusion. Weighted gene co-expression network analysis (WGCNA) was used to identify related genes. A protein–protein interaction network containing 85 overlapping DEGs and WGCNA genes was constructed. Using Molecular Complex Detection and cytoHubba plug-ins in Cytoscape and Kyoto Encyclopedia of Genes and Genomes analyses, we identified 5 core pathways and 13 hub genes (IL-1β, JUN, TNFAIP3, CCL2, ICAM1, CCL20, SOCS3, IRF1, BIRC3, GADD45B, MYC, CCL4, and BCL2A1). These findings were validated using two independent datasets (GSE14951 and GSE15480) and a mouse LIRI model, which effectively confirmed the expression levels of 13 hub genes. This study aimed to use advanced bioinformatics methods to investigate hub genes related to LIRI to identify new biomarkers and improve our understanding of LIRI pathogenesis.