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目的:利用基因表达谱芯片研究局灶性皮质发育不良(FCD)病变组织和正常脑组织中差异表达的基因,探讨FCD可能的发病机制。方法:收集FCD患者病变脑组织(病例组)及正常人(对照组)脑组织各3例,抽提总RNA,利用Affymetrix基因表达谱芯片分析病例组与对照组差异表达的基因;Real-time q PCR验证芯片结果;生物信息学分析差异表达基因参与的相关信号通路,预测FCD可能的致病机制。结果:通过对FCD组织和正常脑组织的基因表达谱的比较分析,发现在FCD组织中C21or F2、AU152162表达上调,ENPP2、ANLN、IP6K3、UGT8、AZGP1表达下调。Real-time qPCR验证表明,ENPP2、ANLN、IP6K3、UGT8、AZGP1基因在病例组和对照组中的表达差异具有统计学意义(P<0.05)。生物信息学分析表明,ENPP2、UG T8、AZGP1蛋白定位于细胞膜或者分泌到细胞外基质,可能通过涉及到脂质代谢以及溶血磷脂酸(LPA)信号通路途径参与髓鞘的形成和神经系统的发育。结论:ENPP2、UGT8、AZGP1基因表达下调,可能通过影响髓鞘的形成及LPA信号通路参与FCD的发生,这些基因参与FCD发生的具体致病机制有待进一步研究。
OBJECTIVE: To study differentially expressed genes in focal cortical dysplasia (FCD) and normal brain using gene expression profiling and to explore the possible pathogenesis of FCD. Methods: Three cases of brain tissue of diseased patients (case group) and normal persons (control group) were collected from FCD patients. Total RNA was extracted and the genes differentially expressed between case group and control group were analyzed by Affymetrix gene expression microarray. Real-time q PCR was used to verify the results of the chip; bioinformatics analysis of the differential signaling genes involved in the signaling pathways to predict the possible pathogenesis of FCD. RESULTS: The gene expression profiles of FCD and normal brain tissues were compared and analyzed. The results showed that the expression of C21or F2 and AU152162 were up-regulated and the expressions of ENPP2, ANLN, IP6K3, UGT8 and AZGP1 were down-regulated in FCD tissues. Real-time qPCR showed that the expression of ENPP2, ANLN, IP6K3, UGT8 and AZGP1 in the cases and controls were significantly different (P <0.05). Bioinformatics analysis showed that ENPP2, UG T8 and AZGP1 localized in the cell membrane or secreted to the extracellular matrix, which may be involved in the formation of myelin and the development of the nervous system by involving the lipid metabolism and the lysophosphatidic acid (LPA) signaling pathway . CONCLUSIONS: The down-regulation of ENPP2, UGT8 and AZGP1 gene may be involved in the development of FCD through influencing the formation of myelin and LPA signaling pathway. The specific pathogenesis of these genes involved in FCD remains to be further studied.