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Updated: Aug 8, 2026
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Evaluation of a Reliable Biomarker in a Cecal Ligation and Puncture-Induced Mouse Model of Sepsis
Published on: December 9, 2022
Identifying GADD45A as a potential R-loop regulator in sepsis via machine-learning and multi-omics analysis
Min Chen1, Jie-Xiang Kang, Shi-Ling He
1Department of Anesthesiology, the Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, China, 362000.
Shock (Augusta, Ga.)
|August 6, 2026
Summary
Sepsis involves immune dysfunction, potentially linked to R-loop accumulation and DNA damage. GADD45A may drive sepsis progression by increasing these factors, making it a diagnostic and prognostic biomarker.
Area of Science:
- Molecular biology
- Immunology
- Genetics
Background:
- Sepsis is a critical condition with unclear immune dysfunction mechanisms.
- R-loop accumulation and DNA damage are implicated in immune disorders but understudied in sepsis.
Purpose of the Study:
- To investigate the role of R-loop-related genes (RLRGs) in sepsis.
- To identify potential diagnostic and prognostic biomarkers for sepsis.
Main Methods:
- Integrated multiple gene expression datasets and applied weighted gene co-expression network analysis (WGCNA).
- Utilized machine learning to identify key sepsis-related genes and construct a diagnostic model.
- Validated findings through nomogram construction, single-cell RNA sequencing, survival analysis, and experimental models.
Main Results:
- Identified five overlapping RLRGs (EXOSC4, GADD45A, HMGB2, LDHA, PRKDC), with GADD45A showing significant association with poor survival.
- GADD45A was upregulated in a sepsis mouse model and its silencing reduced inflammatory markers, R-loop accumulation, and DNA damage in cell lines.
- A five-gene nomogram demonstrated clinical utility for sepsis diagnosis.
Conclusions:
- GADD45A is a potential biomarker for sepsis diagnosis and prognosis.
- GADD45A may exacerbate sepsis by promoting R-loop accumulation and DNA damage.