Screening and identification of key gene in sepsis development

Abstract

Sepsis is one of the leading causes of mortality in intensive care units (ICU). The growing incidence rate of sepsis and its high mortality rate result are very important sociosanitary problems. Sepsis is a result of infection which can cause systemic inflammatory and organ failure. But the pathogenesis and the molecular mechanisms of sepsis is still not well understood. The aim of the present study was to identify the candidate key genes in the progression of sepsis. Microarray datasets GSE28750, GSE64457, and GSE95233 were downloaded from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified, and function enrichment analyses were performed. The protein–protein interaction network (PPI) was constructed and the module analysis was performed using STRING and Cytoscape. Furthermore, to verify the results of the bioinformatics analyses, the expression levels of selected DEGs were quantified by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) in libobolysaccharide (LPS)-induced Human Umbilical Vein Endothelial Cells (HUVECs) to support the result of bioinformatics analysis. Thirteen hub genes were identified and biological process analysis revealed that these genes were mainly enriched in apoptotic process, inflammatory response, innate immune response. Hub genes with high degrees, including MAPK14, SLC2A3, STOM, and MMP8, were demonstrated to have an association with sepsis. Furthermore, RT-PCR results showed that SLC2A3 and MAPK14 were significantly upregulated in the HUVECs induced by LPS compared with controls. In conclusion, DEGs and hub genes identified in the present study help us understand the molecular mechanisms of sepsis, and provide candidate targets for diagnosis and treatment of sepsis.

Genetic Variants of Matrix Metalloproteinase and Sepsis: The Need Speed Study

“…MMP-8 is mainly expressed in neutrophils or macrophages, while at later stages of acute lung injury, it can be released from mesenchymal cells in the airways [ 26 ]. MMP-8 is upregulated in sepsis [ 27 ], although laboratory models and molecular biology only show that its presence ensures neutrophil infiltration in response to lipopolysaccharide [ 28 ], likely through the degradation of LIX CXC chemokines [ 29 ]. This would limit lung inflammation and act as a key mediator in the regulation of innate immunity.…”

MiR-940 Serves as a Diagnostic Biomarker in Patients with Sepsis and Regulates Sepsis-Induced Inflammation and Myocardial Dysfunction

“…Recently, with the deepening of clinical research on sepsis, more and more new biomarkers provide new ideas for early diagnosis of this comorbidity. 21 Existing studies have found that miRNA has many biological functions in cell animal models, and participates in the occurrence and development of many immune disorders. 22 In an investigation of C57BL/6 mice induced by CLP, the raised miR-539-5p reduced the pulmonary injury and inflammation triggered by CLP.…”

Identification of key biomarkers in neonatal sepsis by integrated bioinformatics analysis and clinical validation

“…Fu et al. identified SLC2A3 as a hub gene for sepsis development from three datasets via bioinformatics analysis, and they also revealed that the expression of SLC2A3 was significantly increased in endothelial cells (ECs) upon LPS stimulation ( Fu et al., 2020 ). LPS-induced endothelial inflammation plays a vital role in the progression of sepsis.…”