Related Experiment Video
Updated: Sep 4, 2025
Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
Published on: March 15, 2024
Diagnostic and Predictive Values of Ferroptosis-Related Genes in Child Sepsis
Zhi Li1, Chi Zhang2, Yiqi Liu2
1Department of Infectious Diseases, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou, China.
Insights
Early diagnosis of pediatric sepsis is crucial. Ferroptosis-related gene MAPK14 shows significant potential for early sepsis diagnosis in children, improving patient outcomes.
Area of Science:
- Pediatric critical care medicine
- Molecular biology
- Genomics
Background:
- Sepsis in children necessitates early detection to reduce mortality.
- This study investigated the role of ferroptosis-related genes in pediatric sepsis.
Purpose of the Study:
- To identify ferroptosis-related genes associated with sepsis in children.
- To evaluate the diagnostic value of these genes for early sepsis detection.
Main Methods:
- Analyzed microarray data from pediatric sepsis patients to find differentially expressed genes (DEGs).
- Utilized protein-protein interaction networks to identify key genes (hub genes).
- Validated diagnostic potential using training and validation datasets and ELISA.
Main Results:
- Identified 34 ferroptosis-related DEGs, enriched in ferroptosis and hypoxia pathways.
- MAPK14, HMOX1, and TLR4 were identified as hub genes.
- MAPK14 demonstrated high diagnostic accuracy (AUROC 0.935-0.941 in datasets, 0.877 in ELISA).
Conclusions:
- Ferroptosis-related gene MAPK14 is a valuable biomarker for early sepsis diagnosis in children.
- MAPK14 shows promising sensitivity and specificity for identifying pediatric sepsis.
Background:
Early diagnosis of sepsis in children was essential to reducing mortality. This study aimed to explore the value of ferroptosis-related genes in children with sepsis.
Methods:
We screened the septic children microarray dataset from the GEO database and analyzed the ferroptosis-related differentially expressed genes (DEGs). A functional analysis of ferroptosis-related DEGs was performed. The protein-protein interaction network was used to identify hub genes. We explored the immune landscape of sepsis and controls. The value of hub genes in diagnosing sepsis was tested in the training (GSE26440) and validation sets (GSE13904), and ELISA was used to verify their diagnostic value in children with sepsis in our hospital.
Results:
A total of 2,103 DEGs in GSE26440 were obtained, of which ferroptosis-related DEGs were 34. Enrichment analysis showed significant enrichment in the ferroptosis and hypoxia pathways (i.e., HIF-1 pathway). The top three genes (HMOX1, MAPK14, TLR4) were selected as hub genes. Immunological analysis suggested that 10 cell types (i.e., CD8/CD4 T cells) were lower in sepsis. Immune checkpoint-related genes CD274 (PD-L1), HAVCR2 (TIM3), and SIGLEC15 were overexpressed in sepsis. The AUROC for the diagnosis of sepsis for HMOX1 and TLR4 ranged from 0.77 to 0.81, while the AUROC of MAPK14 reached 0.935 and 0.941 in the training and validation sets. Serum ELISA results of HMOX1 and TLR4 showed no significant difference in differentiating sepsis. The AUROC of MAPK14 was 0.877. When the diagnostic threshold was 74.852 ng/ml, the sensitivity and specificity were 0.906 and 0.719, respectively.
Conclusion:
Ferroptosis-related gene MAPK14 is of considerable value in the early diagnosis of sepsis in children.
