Revealing potential signaling pathways and hub genes related to monocytes in sepsis survivors and non-survivors based on single-cell RNA-seq and bulk RNA-seq data

Sepsis is a life-threatening organ dysfunction with a high incidence rate and mortality. The aim of this study was to investigate monocyte-related signaling pathways and hub genes in sepsis survivors and non-survivors. Sepsis-related data were downloaded from Gene Expression Omnibus (GEO) database. Cell annotation and cell communication analysis were performed to identify signaling pathways and ligand-receptor pairs related to monocytes. Immune cell infiltration, functional annotation, differential expression, and correlation analysis were performed to screen for hub genes associated with monocytes. In addition, survival analysis, transcription factors, and drug prediction were also performed on the hub genes. Compared with sepsis survivors, monocytes decreased in sepsis non-survivors. Cell communication results showed that monocytes were also the main signal transmitters and receivers in both the sepsis survivor and the sepsis non-survivor groups. A total of 25 signaling pathways related to monocytes were identified, such as MIF, ANNEXIN, GALECTIN, THBS, ITGB2, CCL, MHC-I, MHC-II, CD23, ICAM, and SEMA4. Subsequently, 6 hub genes (CCR1, CD4, CD47, ITGAX, LILRB1, and PLXNB2) associated with monocytes were identified. Univariate Cox analysis showed that CD4, ITGAX, LILRB1, PLXNB2, and age were associated with the prognosis of sepsis. Multivariate Cox analysis showed that ITGAX and age might be independent prognostic factors for sepsis. ITGAX and CD4 are associated with transcription factors SPI1 and MYB, respectively. Moreover, drug prediction results showed that tregalizumab was an agonist of CD4. This study revealed the monocyte-associated signaling pathways and hub genes, which may contribute to the understanding of the molecular mechanisms of sepsis survivors and non-survivors.