Ferroptosis-associated candidate genes in aneurysmal subarachnoid hemorrhage: evidence from human peripheral blood and mouse brain.
5 affiliations
- 1Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China.
- 2Neurosurgery Third Department, Baoding No.1 Central Hospital, Baoding, Hebei, China.
- 3School of Pharmaceutical Science, University of South China, Hengyang, China.
- 4Department of Neurosurgery, Tianjin Fifth Central Hospital, Tianjin, China.
- 5Department of Neurosurgery, Queen Elizabeth Hospital, Hong Kong, Hong Kong SAR, China.
Abstract
Background
Aneurysmal subarachnoid hemorrhage (aSAH) has high morbidity and mortality. Ferroptosis may contribute to aSAH-related brain injury, but its peripheral and brain-associated signatures remain unclear.Methods
Human peripheral-blood dataset GSE36791 (43 aSAH, 18 controls) was analyzed using limma, FerrDb intersection, WGCNA, GO/KEGG enrichment, and PPI-based prioritization. qPCR validation was performed in peripheral blood from 10 aSAH patients and 10 non-SAH controls; aSAH samples were collected within 24 h after rupture. Mean ages were 60.2 ± 7.7 and 63.6 ± 8.9 years, with 5 and 4 males, respectively. Brain-level validation used GSE79416 mouse cortex and OMIX006611 mouse SAH single-cell RNA-seq data. Male C57BL/6 J mice (8 weeks, 20-22 g) underwent cisterna magna autologous blood injection; brain tissues were collected 1 day after SAH (n = 6/group). Immune infiltration and molecular docking were also performed.Results
Among 2,645 DEGs, 35 were ferroptosis-related. MAPK3, STAT3, G6PD, and PGD were prioritized as ferroptosis-associated candidate genes and were upregulated in human aSAH peripheral blood, mouse SAH cortex, and the clinical qPCR cohort. Single-cell analysis showed expression of the corresponding mouse genes across annotated brain cell types, especially immune/glial populations. In mouse SAH brain tissue, MAPK3/ERK1, STAT3, PGD, and G6PD protein levels increased, p-STAT3/STAT3 ratio was elevated, MDA content increased, and GPX4 activity decreased. Immune profiling showed increased neutrophils, mast cells, and activated dendritic cells. Ganoderic acid A was prioritized as a preliminary in silico candidate.Conclusion
MAPK3, STAT3, G6PD, and PGD are ferroptosis-associated candidate genes in aSAH, supported by human peripheral-blood, mouse cortex, single-cell, and mouse brain validation. Ganoderic acid A remains an exploratory in silico candidate requiring further functional validation.
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BibTeX
@article{li2026ferroptosisassociated,
title = {{Ferroptosis-associated candidate genes in aneurysmal subarachnoid hemorrhage: evidence from human peripheral blood and mouse brain.}},
author = {Jia Li and Cong Wang and Hongwen Li and Yafan Liu and Chunchao Cheng and Zilin Zhao and Guifang Jiang and Xiaopeng Cui and Ben Chat Fong Ng and Yan Zhao and Zhuolin Wu and Xinyu Yang},
journal = {Frontiers in neurology},
year = {2026},
month = oct,
doi = {10.3389/fneur.2026.1823039},
url = {https://europepmc.org/article/MED/42898173},
note = {CC BY},
}
RIS
TY - JOUR
TI - Ferroptosis-associated candidate genes in aneurysmal subarachnoid hemorrhage: evidence from human peripheral blood and mouse brain.
AU - Jia Li
AU - Cong Wang
AU - Hongwen Li
AU - Yafan Liu
AU - Chunchao Cheng
AU - Zilin Zhao
AU - Guifang Jiang
AU - Xiaopeng Cui
AU - Ben Chat Fong Ng
AU - Yan Zhao
AU - Zhuolin Wu
AU - Xinyu Yang
PY - 2026
DA - 2026/10/05
JO - Frontiers in neurology
DO - 10.3389/fneur.2026.1823039
UR - https://europepmc.org/article/MED/42898173
AB - Background Aneurysmal subarachnoid hemorrhage (aSAH) has high morbidity and mortality. Ferroptosis may contribute to aSAH-related brain injury, but its peripheral and brain-associated signatures remain unclear.Methods Human peripheral-blood dataset GSE36791 (43 aSAH, 18 controls) was analyzed using limma, FerrDb intersection, WGCNA, GO/KEGG enrichment, and PPI-based prioritization. qPCR validation was performed in peripheral blood from 10 aSAH patients and 10 non-SAH controls; aSAH samples were collected within 24 h after rupture. Mean ages were 60.2 ± 7.7 and 63.6 ± 8.9 years, with 5 and 4 males, respectively. Brain-level validation used GSE79416 mouse cortex and OMIX006611 mouse SAH single-cell RNA-seq data. Male C57BL/6 J mice (8 weeks, 20-22 g) underwent cisterna magna autologous blood injection; brain tissues were collected 1 day after SAH (n = 6/group). Immune infiltration and molecular docking were also performed.Results Among 2,645 DEGs, 35 were ferroptosis-related. MAPK3, STAT3, G6PD, and PGD were prioritized as ferroptosis-associated candidate genes and were upregulated in human aSAH peripheral blood, mouse SAH cortex, and the clinical qPCR cohort. Single-cell analysis showed expression of the corresponding mouse genes across annotated brain cell types, especially immune/glial populations. In mouse SAH brain tissue, MAPK3/ERK1, STAT3, PGD, and G6PD protein levels increased, p-STAT3/STAT3 ratio was elevated, MDA content increased, and GPX4 activity decreased. Immune profiling showed increased neutrophils, mast cells, and activated dendritic cells. Ganoderic acid A was prioritized as a preliminary in silico candidate.Conclusion MAPK3, STAT3, G6PD, and PGD are ferroptosis-associated candidate genes in aSAH, supported by human peripheral-blood, mouse cortex, single-cell, and mouse brain validation. Ganoderic acid A remains an exploratory in silico candidate requiring further functional validation.
SN - 1664-2295
ER -