Abstract
Patients with metabolic dysfunction-associated steatotic liver disease (MASLD) are more susceptible to liver ischemia-reperfusion injury (LIRI), complicating liver surgery outcomes. This study aimed to uncover shared hub genes and mechanisms linking LIRI and MASLD to enhance donor liver utilization and improve prognosis. Using liver transplantation and MASLD datasets from the Gene Expression Omnibus, we applied Linear Models for Microarray Data and weighted gene co-expression analysis to identify differentially expressed genes and key module genes. Further analysis involved Gene Ontology, KEGG, and machine learning to pinpoint common hub genes and pathways. We identified 5,920 differentially expressed genes in liver datasets and 8,978 across LIRI and MASLD datasets. 71 shared hub genes were associated with pathways like MAPK signaling. Key genes, ADRB2 and CCL2, exhibited correlated mRNA expression in both datasets and human liver tissues. Hypoxia-reoxygenation in MASLD models elevated CCL2 levels and reduced ADRB2 expression. These genes showed strong diagnostic potential (AUC, 0.97). CCL2 knockdown reduced, while ADRB2 knockdown increased, MASLD cells' H/R injury sensitivity. Immune infiltration analysis revealed increased immune cell activity, particularly correlations between M0/M2 macrophages and NK cells/mast cells. ADRB2 and CCL2 were identified as crucial biomarkers, potentially explaining MASLD patients' heightened vulnerability to LIRI during liver transplantation.