Candidate target genes in sepsis diagnosis and therapy: identifying hub genes with a spotlight on KLRB1.

Abstract

Background: Sepsis, which causes systemic inflammation and organ failure, is one of the leading causes of death in the intensive care unit (ICU) and an urgent social health problem. However, the pathogenesis and molecular mechanism of sepsis are unclear. Therefore, this study aimed to identify candidate Hub genes during sepsis progression and the candidate target genes for sepsis diagnosis and treatment.

Methods: GSE54514, GSE57065, GSE69528, GSE95233, and GSE131761 datasets were downloaded from public databases, and the differentially expressed genes (DEGs) between healthy and septic patients in each dataset were screened at adjusted P-value < 0.05 and| log2FC| ≥ 0.58. Subsequently, the obtained DEGs in each dataset were intersected to obtain the Hub genes. In addition, the DEGs between patients with better and poor prognoses in datasets GSE54514 and GSE95233 were analyzed after 28 days. The differential expression of Hub genes in septic patients with good and poor prognoses was detected at adjusted P-value < 0.05 and| log2FC| ≥ 0.58. Finally, real-time quantitative polymerase chain reaction (qRT-PCR) was used to verify the bioinformatics results.

Results: In datasets GSE54514, GSE57065, GSE69528, GSE95233 and GSE131761, RNASE2, RNASE3, CTSG, SLPI, TNFAIP6, PGLYRP1 and BLOC1S1 were up-regulated in septic patients, and RPL10A and KLRB1 were down-regulated compared to healthy controls. qRT-PCR confirmed the expression trend of the hub genes except CTSG (which was not differentially expressed). Compared to septic patients with good prognoses, the differential expression of RNASE3 was higher in patients with poor prognoses. Furthermore, qRT-PCR revealed that KLRB1 was the only differentially expressed hub gene with down-regulated expression in sepsis patients with poor prognosis.

Conclusions: The candidate Hub genes closely related to sepsis include KLRB1, RNASE2, RNASE3, CTSG, SLPI, TNFAIP6, PGLYRP1, BLOC1S1, and RPL10A. KLRB1 is the most relevant candidate hub gene among these hub genes in the molecular underpinnings of sepsis, which could be targeted for sepsis detection and treatment.