{
  "abstract": "Focal cortical dysplasia (FCD) and tuberous sclerosis complex (TSC) are major causes of drug-resistant epilepsy, yet shared molecular mechanisms across these structurally distinct malformations remain poorly characterized. We performed an integrated transcriptomic analysis of RNA-seq data from GSE256068 [85 samples: 64 cortical (FCD2a, FCD2b, TSC, controls) and 21 hippocampal (TLE-HS, controls)]. Differential expression analysis with limma identified 865, 1,915, 2,772, and 3,749 DEGs in FCD2a, FCD2b, TSC, and TLE-HS versus controls, respectively, with 49 shared DEGs across all four subtypes. Weighted gene co-expression network analysis (WGCNA) identified the brown and red modules as key disease-associated modules. By intersecting WGCNA hub genes (|GS| > 0.5, |MM| > 0.8) with shared DEGs, we identified 15 hub genes, all functionally associated with microglia/myeloid lineage, including IRF8, TLR7, CX3CR1, P2RY12, C3AR1, and CCR1. Gene set enrichment analysis (GSEA) revealed 15 KEGG pathways consistently enriched across all subtypes, converging on Toll-like receptor, NF-kB, chemokine, and complement signaling. Immune deconvolution using MCP-counter and xCell confirmed elevated monocytic lineage and T cell infiltration in disease cortex, with monocytic scores showing a positive trend with seizure frequency. A two-gene logistic regression model (CX3CR1 + P2RY12), selected by LASSO and random forest, achieved a training AUC of 0.979 and a nested five-fold cross-validation AUC of 0.862 (95% CI: 0.693–1.000), with an external validation AUC of 0.865 (95% CI: 0.681–1.000) in GSE213488. Drug repurposing via Enrichr identified vorinostat (HDAC inhibitor) as a top candidate, and IRF8 was predicted as the master transcriptional regulator. In vitro , mTOR activation with MHY1485 preserved P2ry12 expression in BV-2 microglia, whereas LPS stimulation induced its loss, supporting a distinct microglia/myeloid-associated program driven by mTOR hyperactivity. These findings demonstrate that cross-subtype transcriptomic convergence on microglial innate immune activation represents a unifying molecular mechanism in FCD and TSC, and that CX3CR1 and P2RY12 together constitute a two-gene diagnostic classifier with encouraging but preliminary performance with potential clinical utility.",
  "abstract_shown": true,
  "affiliations": [
    "Ganzhou Hospital-Nanfang Hospital, Southern Medical University (Ganzhou People’s Hospital)"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 2,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Hongliang Zeng"
    },
    {
      "affs": [
        0
      ],
      "name": "Bin Li"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/agbs5bwzdpv74.bib",
  "cited_by": 0,
  "doi": "10.3389/fnins.2026.1954412",
  "fulltext_url": "https://europepmc.org/articles/PMC13687088",
  "id": "agbs5bwzdpv74",
  "issns": [
    "1662-453X",
    "1662-4548"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fnins.2026.1954412/full",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2738|Epilepsy research and treatment"
    ]
  ],
  "openalex": "W7220974359",
  "pdf_url": "https://europepmc.org/articles/PMC13687088?pdf=render",
  "pmcid": "PMC13687088",
  "pmid": "42922941",
  "published": "2026-10-08",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/agbs5bwzdpv74.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:23Z",
      "native_id": "10.3389/fnins.2026.1954412",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fnins.2026.1954412/full"
    },
    {
      "first_seen": "2026-10-30T12:20:33Z",
      "native_id": "MED:42922941",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42922941"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2738|Epilepsy research and treatment",
      "subfield": "psychiatry"
    }
  ],
  "title": "Identification of microglia-associated hub genes and a CX3CR1/P2RY12 two-gene diagnostic model for cross-subtype epilepsy-associated cortical malformations: integrated transcriptomic analysis with external validation",
  "title_text": "Identification of microglia-associated hub genes and a CX3CR1/P2RY12 two-gene diagnostic model for cross-subtype epilepsy-associated cortical malformations: integrated transcriptomic analysis with external validation",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:33Z",
  "url": "https://research.draconitic.com/paper/agbs5bwzdpv74",
  "venue": "Frontiers in Neuroscience",
  "versions": []
}