Department of Pediatrics, Hebei Medical University, Shijiazhuang, China.
Department of Pediatrics, Hebei General Hospital, Shijiazhuang, China.
Childs Nerv Syst. 2022 May;38(5):953-960. doi: 10.1007/s00381-022-05454-2. Epub 2022 Feb 2.
Focal cortical dysplasia (FCD) is the most common developmental malformation that causes refractory epilepsy. FCD II is a common neuropathological finding in tissues resected therapeutically from patients with drug-resistant epilepsy. However, its molecular genetic etiology remains unclear. This study aimed to identify potential molecular markers of FCD II using bioinformatics analysis.
We downloaded two datasets for FCD II from the Gene Expression Omnibus data repository. Differentially expressed genes (DEGs) between FCD II and normal brain tissues were identified, and functional enrichment analysis was performed. A protein-protein interaction network was constructed, and hub genes were identified from the DEGs. The hub gene expression was validated using WB in vitro. IHC staining was performed to verify the feasibility of the target molecular markers identified in the bioinformatics analysis.
One hundred sixty-seven common DEGs were identified between the datasets. The GO and KEGG analyses showed that variations were prominently enriched in some functions associated with gene expression. Five hub genes (i.e., FANCI, FANCA, BRCA2, RAD18, and KEAP1) were identified. Western blotting confirmed that all hub gene expressions were higher in the FCD II tissue than in the normal brain tissue. IHC staining showed that the FANCI expression significantly increased in the FCD II tissue.
There are DEGs between FCD II and normal brain tissues, which may be considered biomarkers for FCD II, along with FANCI. The DEGs and hub genes identified in the bioinformatics analysis could serve as candidate targets for diagnosing and treating FCD II.
局灶性皮质发育不良（FCD）是导致难治性癫痫的最常见发育性畸形。FCD II 是从耐药性癫痫患者切除的组织中常见的神经病理学发现。然而，其分子遗传病因尚不清楚。本研究旨在使用生物信息学分析鉴定 FCD II 的潜在分子标志物。
我们从基因表达综合数据库中下载了两个 FCD II 的数据集。鉴定 FCD II 与正常脑组织之间的差异表达基因（DEGs），并进行功能富集分析。构建蛋白质-蛋白质相互作用网络，并从 DEGs 中鉴定出枢纽基因。使用体外 WB 验证了 hub 基因的表达。进行免疫组织化学染色以验证生物信息学分析中鉴定出的靶分子标记的可行性。
两个数据集中共鉴定出 167 个常见的 DEGs。GO 和 KEGG 分析表明，与基因表达相关的一些功能显著富集。鉴定出 5 个枢纽基因（即 FANCI、FANCA、BRCA2、RAD18 和 KEAP1）。Western blot 验证表明，FCD II 组织中的所有 hub 基因表达均高于正常脑组织。免疫组织化学染色显示 FANCI 表达在 FCD II 组织中显著增加。
FCD II 与正常脑组织之间存在 DEGs，这些 DEGs 可能与 FANCI 一起作为 FCD II 的生物标志物。生物信息学分析中鉴定出的 DEGs 和枢纽基因可以作为诊断和治疗 FCD II 的候选靶点。
