Identifying hub genes of sepsis-associated and hepatic encephalopathies based on bioinformatic analysis—focus on the two common encephalopathies of septic cirrhotic patients in ICU

In the ICU ward, septic cirrhotic patients are susceptible to suffering from sepsis-associated encephalopathy and/or hepatic encephalopathy, which are two common neurological complications in such patients. However, the mutual pathogenesis between sepsis-associated and hepatic encephalopathies remains unclear. We aimed to identify the mutual hub genes, explore effective diagnostic biomarkers and therapeutic targets for the two common encephalopathies and provide novel, promising insights into the clinical management of such septic cirrhotic patients.

The precious human post-mortem cerebral tissues were deprived of the GSE135838, GSE57193, and GSE41919 datasets, downloaded from the Gene Expression Omnibus database. Furthermore, we identified differentially expressed genes and screened hub genes with weighted gene co-expression network analysis. The hub genes were then subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway functional enrichment analyses, and protein-protein interaction networks were constructed. Receiver operating characteristic curves and correlation analyses were set up for the hub genes. Finally, we explored principal and common signaling pathways by using Gene Set Enrichment Analysis and the association between the hub genes and immune cell subtype distribution by using CIBERSORT algorithm.

We identified seven hub genes—GPR4, SOCS3, BAG3, ZFP36, CDKN1A, ADAMTS9, and GADD45B—by using differentially expressed gene analysis and weighted gene co-expression network analysis method. The AUCs of these genes were all greater than 0.7 in the receiver operating characteristic curves analysis. The Gene Set Enrichment Analysis results demonstrated that mutual signaling pathways were mainly enriched in hypoxia and inflammatory response. CIBERSORT indicated that these seven hub genes were closely related to innate and adaptive immune cells.

We identified seven hub genes with promising diagnostic value and therapeutic targets in septic cirrhotic patients with sepsis-associated encephalopathy and/or hepatic encephalopathy. Hypoxia, inflammatory, and immunoreaction responses may share the common downstream pathways of the two common encephalopathies, for which earlier recognition and timely intervention are crucial for management of such septic cirrhotic patients in ICU.