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Identification of a Four-Gene Signature for Diagnosing Paediatric Sepsis
Yinhui Yao1, Jingyi Zhao2, Junhui Hu1
1Department of Pharmacy, Chengde Medical University Affiliated Hospital, Chengde 067000, China.
Insights
A novel four-gene signature accurately identifies paediatric sepsis, offering a promising biomarker for early diagnosis and improved patient outcomes. This discovery aids in reducing hospitalization and mortality rates in children.
Area of Science:
- Genomics
- Molecular Biology
- Pediatric Medicine
Background:
- Early diagnosis of pediatric sepsis is critical for effective treatment, reducing mortality and hospitalization.
- Existing diagnostic biomarkers for sepsis show significant variability, limiting clinical application.
- Gene expression analysis offers a potential avenue for identifying reliable sepsis biomarkers.
Purpose of the Study:
- To evaluate the diagnostic value of key genes in pediatric sepsis using bioinformatics approaches.
- To identify a robust gene signature for distinguishing pediatric sepsis patients from healthy controls.
Main Methods:
- Utilized the GSE119217 dataset to identify differentially expressed genes (DEGs).
- Applied Weighted Gene Coexpression Network Analysis (WGCNA) to identify relevant gene modules.
- Selected candidate genes using Least Absolute Shrinkage and Selection Operator (LASSO) regression and Support Vector Machine Recursive Feature Elimination (SVM-RFE).
- Validated the diagnostic signature in six independent sepsis datasets and performed a meta-analysis.
Main Results:
- Identified 41 common genes (CGs) between DEGs and WGCNA.
- Developed a four-gene signature (ANXA3, CD177, GRAMD1C, TIGD3) that effectively differentiated pediatric sepsis cases from controls.
- Validated the signature's diagnostic performance across multiple independent datasets.
- Meta-analysis revealed high pooled sensitivity (1.00), specificity (0.98), and area under the curve (1.00).
Conclusions:
- The identified four-gene signature serves as a novel and effective biomarker for diagnosing pediatric sepsis.
- This gene signature holds potential for clinical application in early sepsis detection in children.
- The findings contribute to improving diagnostic accuracy and patient management in pediatric sepsis.
Aim:
Early diagnosis of paediatric sepsis is crucial for the proper treatment of children and reduction of hospitalization and mortality. Biomarkers are a convenient and effective method for diagnosing any disease. However, huge differences among the studies reporting biomarkers for diagnosing sepsis have limited their clinical application. Therefore, in this study, we aimed to evaluate the diagnostic value of key genes involved in paediatric sepsis based on the data of the Gene Expression Omnibus database.
Methods:
We used the GSE119217 dataset to identify differentially expressed genes (DEGs) between patients with and without paediatric sepsis. The most relevant gene modules of paediatric sepsis were screened through the weighted gene coexpression network analysis (WGCNA). Common genes (CGs) were found between DEGs and WGCNA. Genes with a potential diagnostic value in paediatric sepsis were selected from the CGs using least absolute shrinkage and selection operator regression and support vector machine recursive feature elimination. The principal component analysis, receiver operating characteristic curves, and C-index were used to verify the diagnostic value of the identified genes in six other independent sepsis datasets. Subsequently, a meta-analysis of the selected genes was performed to evaluate the value of these genes as biomarkers in paediatric sepsis.
Results:
A total of 41 CGs were selected from the GSE119217 dataset. A four-gene signature composed of ANXA3, CD177, GRAMD1C, and TIGD3 effectively distinguished patients with paediatric sepsis from those in the control group. The signature was verified using six other independent datasets. In addition, the meta-analysis results showed that the pooled sensitivity, specificity, and area under the curve values were 1.00, 0.98, and 1.00, respectively.
Conclusion:
The four-gene signature can be used as new biomarkers to distinguish patients with paediatric sepsis from healthy individuals.
