MULTIPLE MACHINE LEARNING METHODS AND COMPARATIVE TRANSCRIPTOMICS IDENTIFY PIVOTAL GENES FOR ISCHEMIA-REPERFUSION INJURY IN HUMAN DONOR TISSUE UNDERGOING ORTHOTOPIC LIVER TRANSPLANTATION

ABSTRACT Background: Hepatic ischemia-reperfusion injury (HIRI) is a major complication affecting patient prognosis during the period after orthotopic liver transplantation (OLT). Although an increasing number of scientists have investigated the molecular biology of ischemia-reperfusion injury (IRI) during OLT in animal and cellular models in recent years, studies using comprehensive and high-quality sequencing results from human specimens to screen for key molecules are still lacking. Aims: The objective of this study is to explore the molecular biological pathways and key molecules associated with HIRI during OLT through RNA sequencing and related bioinformatics analysis techniques. Methods: The study was done by performing mRNA sequencing on liver tissue samples obtained from 15 cases of in situ liver transplantation patients who experienced ischemia and reperfusion injury within 1 year at Guizhou Medical University, and combined with bioinformatics analysis and machine learning methods, we identified the genes and transcription factors that are closely associated with IRI during in situ liver transplantation surgery. Results: There were 877 differentially expressed genes (DEGs) identified in the included liver samples, of which 817 DEGs were upregulated and 60 were downregulated. Functional enrichment analysis revealed significant enrichment of immune-related terms, such as inflammation, defense responses, responses to cytokines, immune system processes, and cellular activation. In addition, core gene enrichment analysis after cytoHubba screening suggested that liver reperfusion injury might be associated with translation-related elements as a pathway together with protein translation processes. Machine learning with the weighted correlation network analysis screening method identified PTGS2, IRF1, and CDKN1A as key genes in the reperfusion injury process. Conclusions: This study demonstrated that the pathways and genomes whose expression is altered throughout the reperfusion process might be critical for the progression of HIRI during OLT.