A Meta-Analysis of Whole Blood Transcriptome Reveals Association of Increased Neutrophil Activity and T cell Suppression in Sepsis

Abstract

Abstract Sepsis is a multi-organ dysfunction due to an uncontrolled host-response to pathogens, a leading cause of mortality in (Intensive care unit) ICUs. Currently, diagnosis of sepsis is a challenging task, due to lack of specific markers. Understanding underlying mechanism associated with sepsis is essential for marker discovery. We employed meta-analysis approach to study the key genes associated with sepsis pathogenesis and immune regulation. We considered six publically available GEO datasets and analyzed using GEO2R to identify differentially expressed genes. Significant (p-value ≤ 0.05 and log fold change ≤ -1.5 or ≥ + 1.5) common genes from six studies were subjected to network analysis and functional enrichment analysis to identify enriched GO terms, KEGG pathways and hub genes. Gene expression data resulted in 233 DEGs, 146 genes were upregulated and 87 genes were downregulated. Through network and functional enrichment analysis 20 hub genes were identified, 11 genes were upregulated, and nine genes were downregulated. The upregulated genes (CD177, MMP8, ARG1, IL18R1, RETN, LTF, S100A12, S100A8, S1000A9, MMP9 and ELANE) are associated with innate immune system and regulates neutrophil activity. Down-regulated genes (FCERIA, IL7R, CCR7, CX3CR1, CD3G, CD40LG, CD247, CD3E and GZMK) are associated with adaptive immune response, T cell function and antigen processing and presentation. Dysregulation of these genes are found to be associated with immunosuppression and increased inflammatory reaction during sepsis. These genes could be used as potential diagnostic markers and therapeutic targets for sepsis condition.