AUTHOR=Tao Linfeng , Zhu Yue , Wu Lifang , Liu Jun
TITLE=Comprehensive analysis of senescence-associated genes in sepsis based on bulk and single-cell sequencing data
JOURNAL=Frontiers in Molecular Biosciences
VOLUME=10
YEAR=2024
URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2023.1322221
DOI=10.3389/fmolb.2023.1322221
ISSN=2296-889X
ABSTRACT=Background: Sepsis is a pathological state resulting from dysregulated immune response in host during severe infection, leading to persistent organ dysfunction and ultimately death. Senescence-associated genes (SAGs) have manifested their potential in controlling the proliferation and dissemination of a variety of diseases. Nevertheless, the correlation between sepsis and SAGs remains obscure and requires further investigation.
Methods: Two RNA expression datasets (GSE28750 and GSE57065) specifically related to sepsis were employed to filter hub SAGs, based on which a diagnostic model predictive of the incidence of sepsis was developed. The association between the expression of the SAGs identified and immune-related modules was analyzed employing Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) and Microenvironment Cell Populations-counter (MCP-counter) analysis. The identified genes in each cohort were clustered by unsupervised agreement clustering analysis and weighted gene correlation network analysis (WGCNA).
Results: A diagnostic model for sepsis established based on hub genes (IGFBP7, GMFG, IL10, IL18, ETS2, HGF, CD55, and MMP9) exhibited a strong clinical reliability (AUC = 0.989). Sepsis patients were randomly assigned and classified by WGCNA into two clusters with distinct immune statuses. Analysis on the single-cell RNA sequencing (scRNA-seq) data revealed high scores of SAGs in the natural killer (NK) cells of the sepsis cohort than the healthy cohort.
Conclusion: These findings suggested a close association between SAGs and sepsis alterations. The identified hub genes had potential to serve as a viable diagnostic marker for sepsis.