Related Experiment Video
Updated: May 3, 2026
Caspase-3 Activity in the Rat Amygdala Measured by Spectrofluorometry After Myocardial Infarction
Published on: January 12, 2016
Ferroptosis-related gene MAPK3 is associated with the neurological outcome after cardiac arrest
Hong Xiang Hou1, Li Pang1, Liang Zhao2
1Department of Emergency, The First Hospital of Jilin University, Changchun, China.
Background:
Neuronal ferroptosis is closely related to the disease of the nervous system, and the objective of the present study was to recognize and verify the potential ferroptosis-related genes to forecast the neurological outcome after cardiac arrest.
Methods:
Cardiac Arrest-related microarray datasets GSE29540 and GSE92696 were downloaded from GEO and batch normalization of the expression data was performed using "sva" of the R package. GSE29540 was analyzed to identify DEGs. Venn diagram was applied to recognize ferroptosis-related DEGs from the DEGs. Subsequently, The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed, and PPI network was applied to screen hub genes. Receiver operating characteristic (ROC) curves were adopted to determine the predictive value of the biomarkers, and the GSE92696 dataset was applied to further evaluate the diagnostic efficacy of the biomarkers. We explore transcription factors and miRNAs associated with hub genes. The "CIBERSORT" package of R was utilized to analyse the proportion infiltrating immune cells. Finally, validated by a series of experiments at the cellular level.
Results:
112 overlapping ferroptosis-related DEGs were further obtained via intersecting these DEGs and ferroptosis-related genes. The GO and KEGG analysis demonstrate that ferroptosis-related DEGs are mainly involved in response to oxidative stress, ferroptosis, apoptosis, IL-17 signalling pathway, autophagy, toll-like receptor signalling pathway. The top 10 hub genes were selected, including HIF1A, MAPK3, PPARA, IL1B, PTGS2, RELA, TLR4, KEAP1, SREBF1, SIRT6. Only MAPK3 was upregulated in both GSE29540 and GAE92696. The AUC values of the MAPK3 are 0.654 and 0.850 in GSE29540 and GSE92696 respectively. The result of miRNAs associated with hub genes indicates that hsa-miR-214-3p and hsa-miR-483-5p can regulate the expression of MAPK3. MAPK3 was positively correlated with naive B cells, macrophages M0, activated dendritic cells and negatively correlated with activated CD4 memory T cells, CD8 T cells, and memory B cells. Compared to the OGD4/R24 group, the OGD4/R12 group had higher MAPK3 expression at both mRNA and protein levels and more severe ferroptosis.
Conclusion:
In summary, the MAPK3 ferroptosis-related gene could be used as a biomarker to predict the neurological outcome after cardiac arrest. Potential biological pathways provide novel insights into the pathogenesis of cardiac arrest.
Insights
Mitogen-activated protein kinase 3 (MAPK3) is identified as a key ferroptosis-related gene for predicting neurological outcomes after cardiac arrest. This finding offers insights into the mechanisms of cardiac arrest and potential therapeutic targets.
Area of Science:
- Biomedical research
- Neuroscience
- Genetics
Background:
- Neuronal ferroptosis is implicated in nervous system diseases.
- Identifying ferroptosis-related genes is crucial for predicting neurological outcomes post-cardiac arrest.
Purpose of the Study:
- To identify and validate ferroptosis-related genes for predicting neurological outcomes after cardiac arrest.
- To explore the biological pathways and immune cell infiltration associated with these genes.
Main Methods:
- Analysis of cardiac arrest microarray datasets (GSE29540, GSE92696) to identify differentially expressed genes (DEGs).
- Utilized Venn diagrams, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and protein-protein interaction (PPI) networks.
- Assessed biomarker predictive value using Receiver Operating Characteristic (ROC) curves and validated findings at the cellular level.
Main Results:
- Identified 112 overlapping ferroptosis-related DEGs involved in oxidative stress, ferroptosis, apoptosis, and inflammatory pathways.
- Selected 10 hub genes, with Mitogen-activated protein kinase 3 (MAPK3) showing significant upregulation and predictive value (AUC 0.654-0.850).
- MAPK3 expression correlated with specific immune cell populations and was linked to ferroptosis severity in cellular models.
Conclusions:
- MAPK3 serves as a potential biomarker for predicting neurological outcomes following cardiac arrest.
- The identified pathways offer new perspectives on the pathogenesis of cardiac arrest.
