Cortical gene expression: prognostic value for seizure outcome following temporal lobectomy and amygdalohippocampectomy

Abstract

Whole genome analyses were performed to test the hypothesis that temporal cortical gene expression differs between epilepsy patients rendered seizure-free versus non-seizure-free following anterior temporal lobectomy with amygdalohippocampectomy (ATL/AH). Twenty four patients underwent ATL/AH to treat medically intractable seizures of temporal lobe origin (mean age 35.5 years, mean follow-up 42.2 months); they were then dichotomized into seizure-free and non-seizure-free groups. Tissue RNA was isolated from the lateral temporal cortex and gene expression analysis was performed. Whole genome data were analyzed for prognostic value for seizure-free outcome following ATL/AH by logistic regression. Genes that could distinguish seizure outcome groups were identified based on providing an accuracy of >0.90 judging by area under the receiver operating characteristic curve, AUC, with a P value of the slope coefficient of <0.05. Four genes and seven RNA probes were with prognostic value for post-operative seizure-free outcome. Gene expression associated with seizure-free outcome included relative down-regulation of zinc finger protein 852 (ZNF852), CUB domain-containing protein 2 (CDCP2), proline-rich transmembrane protein 1 (PRRT1), hypothetical LOC440200 (FLJ41170), RNA probe 8047763, RNA probe 8126238, RNA probe 8113489, RNA probe 8092883, RNA probe 7935228, RNA probe 806293, and RNA probe 8104131. This study describes the predictive value of temporal cortical gene expression for seizure-free outcome after ATL/AH. Four genes and seven RNA probes were found to predict post-operative seizure-free outcome. Future prospective investigation of these genes and probes in human brain tissue and blood could establish new biomarkers predictive of seizure outcome following ATL/AH.

Keywords: Amygdalohippocampectomy; Gene expression; Neurosurgical genomics; Prognostic factor; Temporal lobectomy.

Conflict of interest statement

of Potential Conflicts of Interest: Conflict of Interest: Drs. Gallek, Skoch and Weinand are co-inventors of U.S. Provisional Patent 61/828,596, “Neurosurgical Genomics”.

Figures

Figure 1

Example conditional probability plots of the ZNF852 gene. Significantly different gene expression was defined as the area under receiver operating characteristic curve > 0.9 and p value < 0.05. Positive (triangle) points represent patients where seizures persisted after AHL/ATL. Shaded curve represents probability of seizure free outcome dependent on expression level