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Identifying the shared genes and their related microRNAs, metabolites, and pathways in ischemic stroke and epilepsy
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  • Published: 10 February 2026

Identifying the shared genes and their related microRNAs, metabolites, and pathways in ischemic stroke and epilepsy

  • Yu Chen1 na1,
  • Shuhong Man2 na1,
  • Qinfeng Li1,
  • Yuelong Ji3,
  • Biwen Peng4,
  • Yansheng Ding1 &
  • …
  • Jian Xu  ORCID: orcid.org/0000-0002-3087-824X1,5 

Scientific Reports , Article number:  (2026) Cite this article

We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Subjects

  • Biomarkers
  • Computational biology and bioinformatics
  • Diseases
  • Genetics
  • Neurology
  • Neuroscience

Abstract

Background This study aimed to identify shared genes between ischemic stroke (IS) and epilepsy and explore underlying mechanisms. Methods Transcriptomic datasets from the GEO database were analyzed using differential expression and weighted gene co-expression network analysis (WGCNA). Hub-shared genes were identified through protein-protein interaction networks, ROC analysis, and expression validation. Upstream miRNAs were predicted. Additionally, untargeted plasma metabolomics was performed on children with epilepsy and healthy controls, followed by differential metabolite analysis and metabolic pathway construction. Results WGCNA revealed 594 epilepsy-related and 2,623 IS-related DEGs, with 38 shared DEGs identified, including IL10RA, CD2, and C3AR1. These genes showed high diagnostic value, with their AUC value > 0.66 in both training and validation datasets. Additionally, hsa-let-7b-5p was predicted to target C3AR1. Metabolomics identified 139 differential metabolites, and C3AR1 was implicated in synaptic vesicle cycle, taste transduction, and nicotine addiction pathways via acetylcholine. Conclusions The shared genes, especially C3AR1 may be a key regulator in the development IS and epilepsy, showing potential as a biomarker for both diseases. However, its diagnostic efficacy requires further clinical validation. Given the complexity of these diseases, future research may focus on identifying a panel of biomarkers rather than relying on a single gene.

Data availability

Data is provided within the manuscript or supplementary information file. Further enquiries can be directed to the corresponding author.

Abbreviations

IS:

Ischemic stroke

IL10RA:

Interleukin 10 Receptor Subunit Alpha

CD2:

Cluster of differentiation 2

C3AR1:

Complement component 3a receptor 1

GEO:

Gene Expression Omnibus

WGCNA:

Weighted gene co-expression network analysis

PPI:

Protein–protein interaction

ROC:

Receiver-operating characteristic

DEG:

Differentially expressed genes

PSE:

Post-stroke epilepsy

DAMP:

Damage-associated molecular patterns

CNS:

Central nervous system

GO:

Gene Ontology

KEGG:

Kyoto Encyclopedia of Genes and Genomes

MF:

Molecular function

CC:

Cellular component

BP:

Biological processes

MNC:

Maximal neighborhood component

MCC:

Maximal clique centrality

EPC:

Edge-percolated component

AUC:

Area under the curve

HMDD:

Human microRNA Disease Database

NK:

Natural killer

CD8:

Cluster of differentiation 8

CD4:

Cluster of differentiation 4

CD2:

Cluster of differentiation 2

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Funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by grants from the China Postdoctoral Science Foundation (Grant No. 2018M642618), the National Natural Science Foundation of China (Grant No. 81401230), the Natural Science Foundation of Shandong Province (Grant No. ZR2019BH056), and Shandong Provincial Medical and Health Science and Technology Project(Grant No.202411001099).

Author information

Author notes

  1. These authors contributed equally: Yu Chen and Shuhong Man.

Authors and Affiliations

  1. Department of Clinical Laboratory, Weifang Maternal and Child Health Hospital, No. 12007, Yingqian Street, High-tech Zone, Weifang, 261011, Shandong, China

    Yu Chen, Qinfeng Li, Yansheng Ding & Jian Xu

  2. Department of Obstetrics and Gynecology, Weifang People’s Hospital, Weifang, 261000, Shandong, China

    Shuhong Man

  3. School of Public Health, Peking University, Beijing, 100191, China

    Yuelong Ji

  4. Department of Physiology, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, China

    Biwen Peng

  5. Wuhan University School of Basic Medical Sciences-Weifang Children’s Neurological Diseases and Innovation Transformation Joint Research Center, Weifang, 261011, Shandong, China

    Jian Xu

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Contributions

Yu Chen and Shuhong Man contributed equally to the conceptualization and design of the study. Yu Chen performed the bioinformatics analysis and data interpretation. Shuhong Man was responsible for drafting the manuscript, supervising the data analysis, and conducting additional experiments and analyses as per the reviewer’s comments. Qingfeng Li and Yuelong Ji assisted in the computational analysis and contributed to the discussion of results. Biwen Peng, Yansheng Ding, and Jian Xu provided critical revisions to the manuscript and helped in the integration of the results. Biwen Peng, Yansheng Ding, and Jian Xu are the corresponding authors, guiding the overall study design, manuscript preparation, and the revision process. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Biwen Peng, Yansheng Ding or Jian Xu.

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Ethics approval and consent to participate

The study was approved by Weifang Maternal and Child Health Hospital, and the guardians of children with epilepsy who provided clinical data signed written informed consent. Experimental procedures involving humans were conducted under the World Medical Association Declaration of Helsinki (2000).

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Chen, Y., Man, S., Li, Q. et al. Identifying the shared genes and their related microRNAs, metabolites, and pathways in ischemic stroke and epilepsy. Sci Rep (2026). https://doi.org/10.1038/s41598-026-39299-5

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  • Received: 08 August 2025

  • Accepted: 04 February 2026

  • Published: 10 February 2026

  • DOI: https://doi.org/10.1038/s41598-026-39299-5

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Keywords

  • Ischemic stroke
  • Epilepsy
  • Shared genes
  • MicroRNA
  • Metabolites
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