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Isolation and Analysis of Traceable and Functionalized Extracellular Vesicles from the Plasma and Solid Tissues
Published on: October 17, 2022
Plasma extracellular vesicles-derived microRNAs provide potential biomarkers in distinguishing between focal cortical
Bocheng Zhou1, Hao Yu1, Chang Liu1
1Pediatric Epilepsy Center, Peking University First Hospital, Beijing, China.
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.
Insights
Researchers identified eight microRNAs (miRNAs) in extracellular vesicles (EVs) that can differentiate focal cortical dysplasia (FCD) subtypes. These circulating miRNAs show promise as non-invasive biomarkers for FCD subtyping, aiding surgical planning and prognosis.
Area of Science:
- Neuroscience
- Molecular Biology
- Biomarker Discovery
Background:
- Focal cortical dysplasia (FCD) requires preoperative pathological information for surgical planning, but non-invasive diagnostic methods are lacking.
- MicroRNAs (miRNAs) within plasma extracellular vesicles (EVs) are explored as potential biomarkers for FCD subtyping.
Purpose of the Study:
- To identify specific microRNAs (miRNAs) in plasma extracellular vesicles (EVs) that can distinguish between FCD Type I and FCD Type II.
- To explore the potential of these miRNAs as non-invasive biomarkers for FCD subtyping.
Main Methods:
- Analysis of miRNA differential expression in plasma EVs and brain tissues from pediatric FCD patients (FCD Type I and II).
- Integration of transcriptome data to identify potential miRNA biomarkers and their downstream target genes.
- Enrichment, protein-protein interaction, and immunohistochemical analyses of target genes.
Main Results:
- Eight differentially expressed miRNAs common to plasma EVs and brain tissue were identified between FCD Type Ia and IIb.
- Target genes were enriched in immune-related functions and cytokine-cytokine receptor, p53, and NF-κB signaling pathways.
- CDKN1A and CD274 proteins were found elevated in FCD IIb lesions compared to FCD Ia.
Conclusions:
- Differentially expressed miRNAs in extracellular vesicles show potential as non-invasive biomarkers for FCD subtyping.
- These miRNAs may guide surgical strategies and outcome prediction, particularly for FCD Type II.
- Investigating EV-mediated immune responses offers insights into FCD pathogenesis and epileptogenic mechanisms.
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