A new pyroptosis-related signature for predicting the immune status and injury of liver ischemia-reperfusion.

Objective: Pyroptosis is a type of programmed cell death. This study aimed to explore the roles of key pyroptosis-related genes in liver ischemia-reperfusion injury.

Methods: After collection and standardization of the transcriptome data from GSE12720 database, differentially expressed pyroptosis-related genes were identified. The risk genes screened by a random forest model were used to establish the line graph model. Consensus clustering was used to classify all samples according to the differentially expressed pyroptosis-related genes. Single-sample Gene Set Enrichment Analysis (ssGSEA) was performed to investigate the immune cell infiltration after hepatic ischemia-reperfusion. Cytoscape was used to visualize the regulatory network of transcription factor (TF)-microRNA (miRNA)-target genes.

Results: We identified 18 significantly and differentially expressed pyroptosis-related genes between the disease and normal samples. Among these 18 genes, IL1β was positively correlated with CXCL8 (r = 0.791) and BIRC3 (r = 0.78), while ADORA3 was negatively correlated with GZMB (r = -0.567) and CXCL8 (r = -0.566). Furthermore, the random forest model constructed using the top 10 pyroptosis-related genes could predict the risk of hepatic ischemia-reperfusion. Importantly, the decision curve analysis showed that patients could benefit from the risk prediction model. Moreover, we found that the expression of TXNIP, IRF1, and GJA1 was the mostly regulated by miRNAs, while the expression of BIRC3, NFκB1, and TXNIP was regulated by the TF RELA. RELA had the most hub genes involved in the regulation.

Conclusion: Our study provides an overview of the expression landscape and the functional significance of pyroptosis-related genes in liver ischemia-reperfusion. Our findings also shed light on the clinical application of pyroptosis-related genes in the treatment of hepatic ischemia-reperfusion injury.