A Five-Gene PANoptosis Signature Correlates with Immune Infiltration and Secondary Brain Injury in Intracerebral Hemorrhage.
Overview
- Shenshan Medical Center, Memorial Hospital of Sun Yat-Sen University, Shanwei, Guangdong, People’s Republic of China
- Guangdong Provincial Key Laboratory of Cancer Pathogenesis and Precision Diagnosis and Treatment, Shenshan Medical Center, Memorial Hospital of Sun Yat-Sen University, Shanwei, Guangdong, People’s Republic of China
- Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China
- Department of Neurosurgery, Shenshan Medical Center, Memorial Hospital of Sun Yat-Sen University, Shanwei, Guangdong, People’s Republic of China
Abstract
Objective: Primary intracerebral hemorrhage (ICH) is a severe stroke subtype characterized by high mortality and disability rates, largely attributable to secondary brain injury (SBI). While programmed cell death (PCD) pathways contribute to SBI, their mechanisms remain incompletely understood. This research investigated PANoptosis, a newly defined integrated PCD pathway, and its interactions with immune responses in ICH.
Methods: The transcriptomic dataset GSE24265 was analyzed to identify differentially expressed genes (DEGs), which were intersected with a PANoptosis-related gene set. PANoptosis-related DEGs were analyzed through protein-protein interaction (PPI) networks, functional enrichment, and machine learning (LASSO and Random Forest) to identify signature genes. The diagnostic utility was evaluated using nomograms and receiver operating characteristic (ROC) curves. Immune interactions were assessed using CIBERSORT. Key findings were validated in clinical specimens using qRT-PCR and Western blot.
Results: We identified 50 PANoptosis-related DEGs in ICH and derived five signature genes (AKR1C2, SLC2A14, FTL, TNFRSF12A, and SLC2A3) that were significantly upregulated and had high diagnostic accuracy. These genes were implicated in an inflammatory cell death hub, as their expression correlated with altered proportions of T follicular helper and T gamma delta cells, linking PANoptosis to immune dysregulation. Experimental validation confirmed the upregulation of mRNA levels of SLC2A3, SLC2A14, and TNFRSF12A in perihematomal tissues, along with increased protein levels of SLC2A3 and SLC2A14. Functional enrichment analysis linked these genes to HIF-1, NF-κB, and TNF signaling pathways in ICH PANoptosis.
Conclusion: Our study identifies PANoptosis as a pathological hub connecting SBI and neuroinflammation in ICH, with five signature genes serving as key diagnostic biomarkers. Notably, SLC2A3 was significantly elevated in peripheral blood, highlighting its potential as a non-invasive plasma biomarker for ICH. These genes likely contribute to neuroinflammation through immune crosstalk and metabolic reprogramming, offering novel mechanistic insights and potential therapeutic targets for SBI post-ICH.
Reproduced under the paper's license (CC BY-NC), from the paper cited above.
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Data
Data links
- ncbi.nlm.nih.gov/
geo , NCBI; found in the text, “Data Acquisition”
Data Sharing Statement
The original results presented in this study are available from the corresponding author on request.
Reproduced under the paper's license (CC BY-NC), from the paper cited above.
Versions
The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.
Version 1, 30 September 2026: the first record
Recorded: type, language, journal, volume, pages, dates, 6 authors, 4 keywords, 1 funder, 60 references.
Cite
This paper
Chen, Z., Zhang, X., Deng, Z., Luo, J., Han, C., & Weng, Y. (2026). A Five-Gene PANoptosis Signature Correlates with Immune Infiltration and Secondary Brain Injury in Intracerebral Hemorrhage. International journal of general medicine, 19, 581629. https://
BibTeX
@article{chen2026five,
author = {Chen, Zhaohui and Zhang, Xueyuan and Deng, Zhicheng and Luo, Jiali and Han, Chunyang and Weng, Yinlun},
title = {{A Five-Gene PANoptosis Signature Correlates with Immune Infiltration and Secondary Brain Injury in Intracerebral Hemorrhage}},
journal = {International journal of general medicine},
year = {2026},
month = mar,
volume = {19},
pages = {581629},
publisher = {Dove Press},
issn = {1178-7074},
doi = {10.2147/
url = {https://
pmid = {41821641},
pmcid = {PMC12977075}
}
RIS
TY - JOUR
AU - Chen, Zhaohui
AU - Zhang, Xueyuan
AU - Deng, Zhicheng
AU - Luo, Jiali
AU - Han, Chunyang
AU - Weng, Yinlun
TI - A Five-Gene PANoptosis Signature Correlates with Immune Infiltration and Secondary Brain Injury in Intracerebral Hemorrhage
T2 - International journal of general medicine
J2 - Int J Gen Med
PY - 2026
DA - 2026/
VL - 19
SP - 581629
SN - 1178-7074
PB - Dove Press
DO - 10.2147/
UR - https://
LA - en
ER -
CSL-JSON
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