Commonly expressed key transcriptomic profiles of sepsis in the human circulation and brain via integrated analysis

Sepsis is the leading cause of death in intensive care units and is characterized by multiple organ failure, including dysfuction of the immune system and brain. This study aims to determine the differential effect of sepsis on specific circulating immune cell subsets compared with brain transcriptome and identify the genes co-expressed by them, so as to identify key genes and regulatory factors involved in the pathogenesis of sepsis induced brain injury and identify novel therapeutic targets.

The GSE133822 and GSE135838 datasets were obtained from the Gene Expression Omnibus (GEO) database and utilized for bioinformatics analyses. Functional enrichment analysis was used to identify commonly expressed genes that were differentially expressed between sepsis patients and non-sepsis patients with critical illness; protein-protein interaction (PPI) networks were also generated. Then, key transcriptomic biomarkers were further validated in an external dataset from the GEO. We also investigated the expression of key mRNAs in peripheral blood mononuclear cells (PBMCs) from sepsis patients by quantitative PCR (qPCR) and an in-vitro model stimulated by lipopolysaccharide (LPS) was generated in brain cell lines.

The transcriptomic profiles of brain tissue were relatively similar as those of specific immune cells. In addition, our validation showed that these key genes were up regulated both in PBMCs in sepsis patients and LPS-treated brain cells.

Brain injury in sepsis was correlated with circulating immune responses, and the expression of DEFA3, MMP8, MMP9 and LCN2 might be potential diagnostic biomarkers as well as therapeutic target in septic brain dysfunction.