Fig. 4: miRNAs profiles and target analysis of differentially expressed miRNAs in plasma EVs of FCD Ia and IIb groups.

a The heatmap of differently expressed miRNA in plasma EVs of FCD Ia and IIb. hsa-miR-34a-5p, hsa-miR-455-3p, hsa-miR-873-5p, and hsa-miR-511-5p are the four miRNAs that showed high expression in FCD IIb. FCD Ia showed high expression of five miRNAs: hsa-miR-96-5p, hsa-miR-9-5p, hsa-miR-183-5p, hsa-miR-381-3p, and X_438/4. Except for X_438/4, all miRNAs were known. b The heatmap of differently expressed miRNA in brain tissue of FCD Ia and IIb. There are 20 miRNAs highly expressed in FCD IIb and 36 miRNAs highly expressed in FCD Ia. All are known miRNAs except 1_1174 and 8_17830. c The bubble plot of GOs enriched, including Biological Process (BP), Cellular Component (CC), and Molecular Function (MF). Target genes were selected from the database to identify those that were differentially expressed in the brain tissue of FCD Ia and IIb groups and that interacted with the eight DEMs in plasma EVs. d The bubble plot of KEGG pathways enriched. e The Venn plot showed the relationship between miRNA expression in plasma EVs and brain tissue. Circle A represents miRNAs expressed in plasma EVs; circle B represents DEMs in plasma EVs of FCD Ia and IIb; circle C represents miRNAs expressed in brain tissue; and circle D represents DEMs in brain tissue of FCD Ia and IIb. 828 miRNAs were identified in plasma EVs, and 703 miRNAs were expressed in brain tissue, 8 of which were differently expressed in plasma EVs. hsa-miR-34a-5p is differentially expressed in both plasma EVs and brain tissue of FCD Ia and IIb. f Immunohistochemistry of CDKN1A and CD274 in FCD lesions. These two immunoregulatory proteins exhibited strong positivity in FCD IIb but lower expression in FCD Ia. g Protein-protein interaction network analysis of downstream target genes, ranked and visualized based on degree centrality. The core network comprised nine hub proteins, with ICAM1 displaying the highest degree, followed by CD274, CXCL10, FOS, IL7R, ANXA2, CDKN1A, RUNX1, and CHEK1. Abbreviations: FCD, focal cortical dysplasia; EVs, extracellular vesicles; DEMs, differential expression miRNAs; GO, Gene Ontology; KEGG, Kyoto Encyclopedia of Genes and Genomes.