A signature of immune-related genes correlating with clinical prognosis and immune microenvironment in sepsis

Abstract

Background Immune-related genes (IRGs) remain poorly understood in their function in the onset and progression of sepsis. Methods GSE65682 was obtained from the Gene Expression Omnibus database. The IRGs associated with survival were screened for subsequent modeling using univariate Cox regression analysis and least absolute shrinkage and selection operator in the training cohort. Then, we assessed the reliability of the 7 IRGs signature's independent predictive value in the training and validation cohorts following the creation of a signature applying multivariable Cox regression analysis. After that, we utilized the E-MTAB-4451 external dataset in order to do an independent validation of the prognostic signature. Finally, the CIBERSORT algorithm and single-sample gene set enrichment analysis was utilized to investigate and characterize the properties of the immune microenvironment. Results Based on 7 IRGs signature, patients could be separated into low-risk and high-risk groups. Patients in the low-risk group had a remarkably increased 28-day survival compared to those in the high-risk group (P < 0.001). In multivariable Cox regression analyses, the risk score calculated by this signature was an independent predictor of 28-day survival (P < 0.001). The signature's predictive ability was confirmed by receiver operating characteristic curve analysis with the area under the curve reaching 0.876 (95% confidence interval 0.793–0.946). Moreover, both the validation set and the external dataset demonstrated that the signature had strong clinical prediction performance. In addition, patients in the high-risk group were characterized by a decreased neutrophil count and by reduced inflammation-promoting function. Conclusion We developed a 7 IRGs signature as a novel prognostic marker for predicting sepsis patients’ 28-day survival, indicating possibilities for individualized reasonable resource distribution of intensive care unit.

Identification of qualitative characteristics of immunosuppression in sepsis based on immune-related genes and immune infiltration features

“…Immunosuppression, particularly post-clinical 'recovery,' has been identified as a crucial factor [ [10] , [11] , [12] , [13] ]. Previous evidence has demonstrated that analyzing the differential expression of immune-related genes (IRGs) in sepsis aids in identifying biomarkers for early prediction and diagnosis [ [14] , [15] , [16] , [17] , [18] ]. Therefore, IRGs hold promise as potential biomarkers for predicting and treating sepsis.…”

Acacetin protects against sepsis-induced acute lung injury by facilitating M2 macrophage polarization via TRAF6/NF-κB/COX2 axis

“… 9 Another work has shown that the infiltration of inflammatory cells and the release of pro-inflammatory mediators play a significant role in ALI development. 10 Macrophages, as the first line of defense of lung immune defense, are broadly distributed on the surface of airways and alveoli. Macrophages play vital roles in ALI via cytokines and chemokines release.…”