Identification of distinct immune infiltration and potential biomarkers in patients with liver ischemia-reperfusion injury

Abstract

Aims: To identify alterations of specific gene expression, immune infiltration components, and potential biomarkers in liver ischemia-reperfusion injury (IRI) following liver transplantation (LT).

Materials and methods: GSE23649 and GSE151648 datasets were obtained from the Gene Expression Omnibus (GEO) database. To determine the differentially expressed genes (DEGs), we utilized the R package "limma". We also identify the infiltration of different immune cells through single-sample gene-set enrichment analysis (ssGSEA). Furthermore, we utilized LASSO logistic regression to select feature genes and Spearman's rank correlation analysis to determine the correlation between these genes and infiltrating immune cells. Finally, the significance of these feature genes was confirmed using a mouse model of hepatic IRI.

Key findings: A total of 17 DEGs were acquired, most of which were associated with inflammation, apoptosis, cell proliferation, immune disorders, and cellular response. 28 immune cell types were determined using ssGSEA. 5 feature genes (ADM, KLF6, SERPINE1, SLC20A1, and HBB) were screened using LASSO analysis, but the HBB gene was ultimately excluded due to the lack of statistical significance in the GSE151648 dataset. These 4 feature genes were predominantly related to immune cells. Finally, 15 significantly distinctive types of immune cells between the control and IRI groups were verified.

Significance: We unveiled that macrophages, dendritic cells (DCs), neutrophils, CD4 T cells, and other immune cells infiltrated the IRI that occurred after LT. Moreover, we identified ADM, KLF6, SERPINE1, and SLC20A1 as potential biological biomarkers underlying IRI post-transplant, which may improve the diagnosis and prognosis of this condition.

Keywords: Bioinformatics; Immunity; Inflammation; Ischemia and reperfusion injury; Liver transplantation.