Biological Information Analysis on the Correlation between Sepsis and Cognitive Dysfunction

Abstract

Background: Sepsis and mild cognitive impairment (MCI) are two distinct clinical conditions that often interact in their progression. However, the potential shared pathological mechanisms of these two diseases are yet to be explored. This study aims to investigate differentially expressed genes (DEGs) in sepsis and cognitive dysfunction using biological data methods. The goal is to delve into their shared genetic characteristics and underlying molecular mechanisms, providing innovative ideas for the treatment of sepsis in combination with MCI. Methods: Gene expression profiles for sepsis (GSE131761) and cognitive dysfunction (GSE63060) were accessed from the gene expression omnibus (GEO) database. The data were analyzed using R software (version 4.3.2, R Core Team, Vienna, Austria) to identify DEGs between sepsis and MCI. Furthermore, annotation of the biological pathways was performed using the gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analysis. Additionally, the STRING database and Cytoscape software were employed to construct a protein-protein interaction (PPI) network and screen the key genes. Finally, the hub genes were validated using external datasets (GSE46955, GSE63061, GSE137342). Results: It was found that 36 DEGs were shared between sepsis and MCI. Furthermore, biological processes were significantly enriched within key pathways such as cellular respiration, oxidative phosphorylation, aerobic respiration, and ATP synthesis coupled electron transport. In terms of cellular components, these DEGs were enriched in the inner mitochondrial membrane protein complex, respiratory chain complex, mitochondrial respirasome, and mitochondrial protein-containing complex. Regarding molecular function, they were enriched in structural constituent of ribosome, Nicotinamide adenine dinucleotide (NADH) dehydrogenase activity, and oxidoreductase activity. Furthermore, the KEGG analysis enriched these genes in Parkinsons disease, oxidative phosphorylation, thermogenesis, neurodegeneration, and prion disease. The PPI network analysis revealed 10 hub genes, including cytochrome c oxidase subunit 7C (COX7C), NADH:ubiquinone oxidoreductase subunit B3 (NDUFB3), ubiquinol-cytochrome c reductase complex III subunit VII (UQCRQ), cytochrome c oxidase subunit 7A2 (COX7A2), NDUFA4 mitochondrial complex associated (NDUFA4), ATP synthase peripheral stalk subunit F6 (ATP5PF), NADH:ubiquinone oxidoreductase subunit A1 (NDUFA1), SRA stem-loop interacting RNA binding protein (SLIRP), cytochrome c oxidase copper chaperone COX17 (COX17) and small nuclear ribonucleoprotein polypeptide G (SNRPG). The validation results with external datasets showed that reduced efficiency of oxidative phosphorylation was a common mechanism of sepsis and MCI. Conclusion: This study identified pathological mechanisms between sepsis and MCI. Moreover, this study identified key genes and their regulatory pathways, and their core mechanisms might be linked to oxidative phosphorylation, providing a theoretical basis for understanding their genetic linkage, and offering innovative ideas for future research.