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Background <p>Preoperative pathological information of focal cortical dysplasia (FCD) is critical for surgical planning, but non-invasive diagnostic methods are currently unavailable. This study aimed to identify potential biomarkers for FCD subtyping by screening microRNAs (miRNAs) in plasma extracellular vesicles (EVs).</p> Methods <p>We identified the most representative pathological subtypes based on the clinical characteristics of FCD Type I and II in 439 pediatric FCD patients. Differential expression analysis of miRNA was performed in plasma EVs and brain tissues from samples of representative pathological subtypes. Potential biomarkers and downstream target genes were identified by integrating brain tissue transcriptome data. Target genes underwent enrichment and protein-protein interaction analyses, with immunohistochemical validation in brain tissue.</p> Results <p>FCD Ia and IIb represent the clinical characteristics between FCD Type I and II, respectively. Eight differentially expressed miRNAs common to plasma EVs and brain tissue were identified, which had 241 target genes in brain tissue. These target genes were enriched in immune-related functions, cytokine-cytokine receptor interaction, p53, and NF-κB signaling pathways. Among nine core proteins, CDKN1A and CD274 were confirmed to be elevated in FCD IIb lesions compared to FCD Ia.</p> Conclusion <p>Differentially expressed miRNAs in extracellular vesicles may serve as potential non-invasive biomarkers for FCD subtyping.</p> Impact <p><UnorderedList Mark="Bullet"> <ItemContent> <p>Lesional characteristics, surgical approaches, and prognosis are different between FCD type I and II.</p> </ItemContent> <ItemContent> <p>Eight differentially expressed miRNAs in plasma extracellular vesicles between FCD type I and II were identified.</p> </ItemContent> <ItemContent> <p>Target genes of these miRNAs were significantly enriched in immune and inflammatory responses and cytokine pathways.</p> </ItemContent> <ItemContent> <p>The identified miRNAs may represent potential pre-operative biomarkers for FCD subtyping, potentially guiding surgical strategies and outcome prediction, especially for FCD type II.</p> </ItemContent> <ItemContent> <p>Extracellular vesicle-mediated immune responses may differ between FCD type I and II, offering insight into FCD pathogenesis, epileptogenic mechanisms, and the identification of novel therapeutic targets.</p> </ItemContent> </UnorderedList></p>

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Plasma extracellular vesicles-derived microRNAs provide potential biomarkers in distinguishing between focal cortical dysplasia type I and II

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月2日

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  • Bocheng Zhou,
  • Hao Yu,
  • Chang Liu,
  • Yao Wang,
  • Yi Wang,
  • Ruofan Wang,
  • Qingzhu Liu,
  • Taoyun Ji,
  • Shuang Wang,
  • Huili Wang,
  • Ye Wu,
  • Xiaoyan Liu,
  • Yuwu Jiang,
  • Lixin Cai,
  • Yu Sun

摘要

Background

Preoperative pathological information of focal cortical dysplasia (FCD) is critical for surgical planning, but non-invasive diagnostic methods are currently unavailable. This study aimed to identify potential biomarkers for FCD subtyping by screening microRNAs (miRNAs) in plasma extracellular vesicles (EVs).

Methods

We identified the most representative pathological subtypes based on the clinical characteristics of FCD Type I and II in 439 pediatric FCD patients. Differential expression analysis of miRNA was performed in plasma EVs and brain tissues from samples of representative pathological subtypes. Potential biomarkers and downstream target genes were identified by integrating brain tissue transcriptome data. Target genes underwent enrichment and protein-protein interaction analyses, with immunohistochemical validation in brain tissue.

Results

FCD Ia and IIb represent the clinical characteristics between FCD Type I and II, respectively. Eight differentially expressed miRNAs common to plasma EVs and brain tissue were identified, which had 241 target genes in brain tissue. These target genes were enriched in immune-related functions, cytokine-cytokine receptor interaction, p53, and NF-κB signaling pathways. Among nine core proteins, CDKN1A and CD274 were confirmed to be elevated in FCD IIb lesions compared to FCD Ia.

Conclusion

Differentially expressed miRNAs in extracellular vesicles may serve as potential non-invasive biomarkers for FCD subtyping.

Impact

Lesional characteristics, surgical approaches, and prognosis are different between FCD type I and II.

Eight differentially expressed miRNAs in plasma extracellular vesicles between FCD type I and II were identified.

Target genes of these miRNAs were significantly enriched in immune and inflammatory responses and cytokine pathways.

The identified miRNAs may represent potential pre-operative biomarkers for FCD subtyping, potentially guiding surgical strategies and outcome prediction, especially for FCD type II.

Extracellular vesicle-mediated immune responses may differ between FCD type I and II, offering insight into FCD pathogenesis, epileptogenic mechanisms, and the identification of novel therapeutic targets.