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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.

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Acknowledgments

The authors would like to acknowledge the following funding used to make this manuscript possible.

Weinand M, Co-PI, received support for purchase of laboratory materials from RO1MH065151 (Yuri Persidsky, Temple University) (HCS 04-42), NIH subcontract from Temple University to University of Arizona

Gallek M received salary support from Robert Wood Johnson Nurse Faculty Scholar Grant # 70318.

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Correspondence to Matthew J. Gallek.

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Conflict of interest

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

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. IRB# 1401194084, The University of Arizona.

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Gallek, M.J., Skoch, J., Ansay, T. et al. Cortical gene expression: prognostic value for seizure outcome following temporal lobectomy and amygdalohippocampectomy. Neurogenetics 17, 211–218 (2016). https://doi.org/10.1007/s10048-016-0484-2

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Keywords

  • Gene expression
  • Temporal lobectomy
  • Prognostic factor
  • Amygdalohippocampectomy
  • Neurosurgical genomics