GPX4 is a key ferroptosis biomarker and correlated with immune cell populations and immune checkpoints in childhood sepsis
Abstract Sepsis is the uncontrolled reaction of the body to infection-induced inflammation, which results in life-threatening multiple-organ dysfunction (MODS). Although the research on sepsis has advanced significantly in recent years, its pathophysiology remains entirely unknown. Ferroptosis is a...
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Nature Portfolio
2023-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-32992-9 |
| _version_ | 1797778913735213056 |
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| author | Guoxin Qu Hui Liu Jin Li Siyuan Huang Nannan Zhao Ling Zeng Jin Deng |
| author_facet | Guoxin Qu Hui Liu Jin Li Siyuan Huang Nannan Zhao Ling Zeng Jin Deng |
| author_sort | Guoxin Qu |
| collection | DOAJ |
| description | Abstract Sepsis is the uncontrolled reaction of the body to infection-induced inflammation, which results in life-threatening multiple-organ dysfunction (MODS). Although the research on sepsis has advanced significantly in recent years, its pathophysiology remains entirely unknown. Ferroptosis is a new-fashioned type of programmed cell death that may have an impact on sepsis development. However, the precise mechanism still needs to be explored. In this paper, Four pediatric sepsis datasets [training datasets (GSE26378 and GSE26440) and validation datasets (GSE11755 and GSE11281)] were chosen through the GEO (Gene Expression Omnibus) database, and 63 differentially expressions of ferroptosis-relation-genes (DE-FRGs) were eventually discovered using bioinformatics investigation. Functional annotation was performed using GO and KEGG pathway enrichment analysis. Then, four Core-FRGs (FTH1, GPX4, ACSL1, and ACSL6) were extracted after the construction of the protein–protein interaction (PPI) network and the research of the MCODE module. Consequently, Hub-FRG (GPX4) was found using the validation datasets, and correlation exploration of immunity populations (neutrophils, r = − 0.52; CD8 T-cells, r = 0.43) and immunity checkpoints (CD274, r = − 0.42) was implemented. The usefulness of GPX4 as a marker in sepsis was assessed in a mouse model of sepsis. The findings demonstrate that GPX4 is a crucial biomarker and a new latent immunotherapy target for the prediction and therapy of pediatric sepsis. |
| first_indexed | 2024-03-12T23:24:24Z |
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| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-12T23:24:24Z |
| publishDate | 2023-07-01 |
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| spelling | doaj.art-8d130b55339e45a2a0d6187579869ff42023-07-16T11:14:48ZengNature PortfolioScientific Reports2045-23222023-07-0113111710.1038/s41598-023-32992-9GPX4 is a key ferroptosis biomarker and correlated with immune cell populations and immune checkpoints in childhood sepsisGuoxin Qu0Hui Liu1Jin Li2Siyuan Huang3Nannan Zhao4Ling Zeng5Jin Deng6The First Affiliated Hospital of Hainan Medical University, Hainan Medical UniversityThe First Affiliated Hospital of Hainan Medical University, Hainan Medical UniversityState Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, Army Medical UniversityState Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, Army Medical UniversityThe First Affiliated Hospital of Hainan Medical University, Hainan Medical UniversityState Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, Army Medical UniversityThe Affiliated Hospital of Guizhou Medical University, Guizhou Medical UniversityAbstract Sepsis is the uncontrolled reaction of the body to infection-induced inflammation, which results in life-threatening multiple-organ dysfunction (MODS). Although the research on sepsis has advanced significantly in recent years, its pathophysiology remains entirely unknown. Ferroptosis is a new-fashioned type of programmed cell death that may have an impact on sepsis development. However, the precise mechanism still needs to be explored. In this paper, Four pediatric sepsis datasets [training datasets (GSE26378 and GSE26440) and validation datasets (GSE11755 and GSE11281)] were chosen through the GEO (Gene Expression Omnibus) database, and 63 differentially expressions of ferroptosis-relation-genes (DE-FRGs) were eventually discovered using bioinformatics investigation. Functional annotation was performed using GO and KEGG pathway enrichment analysis. Then, four Core-FRGs (FTH1, GPX4, ACSL1, and ACSL6) were extracted after the construction of the protein–protein interaction (PPI) network and the research of the MCODE module. Consequently, Hub-FRG (GPX4) was found using the validation datasets, and correlation exploration of immunity populations (neutrophils, r = − 0.52; CD8 T-cells, r = 0.43) and immunity checkpoints (CD274, r = − 0.42) was implemented. The usefulness of GPX4 as a marker in sepsis was assessed in a mouse model of sepsis. The findings demonstrate that GPX4 is a crucial biomarker and a new latent immunotherapy target for the prediction and therapy of pediatric sepsis.https://doi.org/10.1038/s41598-023-32992-9 |
| spellingShingle | Guoxin Qu Hui Liu Jin Li Siyuan Huang Nannan Zhao Ling Zeng Jin Deng GPX4 is a key ferroptosis biomarker and correlated with immune cell populations and immune checkpoints in childhood sepsis Scientific Reports |
| title | GPX4 is a key ferroptosis biomarker and correlated with immune cell populations and immune checkpoints in childhood sepsis |
| title_full | GPX4 is a key ferroptosis biomarker and correlated with immune cell populations and immune checkpoints in childhood sepsis |
| title_fullStr | GPX4 is a key ferroptosis biomarker and correlated with immune cell populations and immune checkpoints in childhood sepsis |
| title_full_unstemmed | GPX4 is a key ferroptosis biomarker and correlated with immune cell populations and immune checkpoints in childhood sepsis |
| title_short | GPX4 is a key ferroptosis biomarker and correlated with immune cell populations and immune checkpoints in childhood sepsis |
| title_sort | gpx4 is a key ferroptosis biomarker and correlated with immune cell populations and immune checkpoints in childhood sepsis |
| url | https://doi.org/10.1038/s41598-023-32992-9 |
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