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.

Epilepsy biomarkers – Toward etiology and pathology specificity

“…Most biomarkers, however, are continuous variables (e.g., plasma miRNA levels), and a cutoff value must be defined to determine whether or not a condition is present. Many recent studies have attempted to define "multivariate biomarker signatures", e.g., a combinatory biomarker, reporting on molecular tissue microenvironment (Gallek et al, 2016), multistructure magnetic resonance imaging (MRI) abnormalities (Pitkänen and Immonen, 2014), combined imaging and behavioral abnormalities (Pascente et al, 2016), or combined behavioral abnormalities (Bröer and Löscher, 2015). Although combinatory biomarkers can be useful in some conditions (e.g., response biomarkers), standardization and setting the cutoff values for combinatory biomarker panels is a challenge, as is translation from the laboratory to the clinic.…”

“…One of the studies listed in Table 3 can be considered to fall into the predictive biomarker category. Gallek et al (Gallek et al, 2016) found that a relative downregulation of a set of genes in the lateral temporal cortex serves as a predictive biomarker for seizure-freedom after epilepsy surgery (Table 3).…”

Leukocyte expression profiles reveal gene sets with prognostic value for seizure-free outcome following stereotactic laser amygdalohippocampotomy

“…Our differential expression (DE) data were obtained through the use of RNA-Seq, a next generation sequencing (NGS) method with improved sensitivity and dynamic range compared with microarray-based profiling 10 . Based on our results, we reiterate the concept of “neurosurgical genomics” whereby systemic leukocyte gene expression serves as a prognostic biomarker for successful outcome from operative neurosurgical intervention 11 .…”

“…All patients met the Task Force of the ILAE (International League Against Epilepsy) Commission on Therapeutic Strategies definition of drug-resistant epilepsy. Therefore, each patient had “intractable epilepsy” resistant to at least two well tolerated, appropriately chosen and prescribed anti-epileptic drug regimens either as mono-therapies or in combination 11,48 . This study was approved by and conducted in accordance with the approved protocols and subject consent forms provided by the University of Arizona College of Medicine Institutional Review Board.…”

Recent Developments in Diagnosis of Epilepsy: Scope of MicroRNA and Technological Advancements

“…It had been reported that there is a relative reduction in ZNF852, CDCP2, PRRT1, FLJ41170, and 7RNA probes in patients who become seizure-free, after lobectomy for interactable TLE patients [ 224 ]. An amplified hippocampal myoinositol/total creatine ratio is a potential diagnostic biomarker for epileptogenesis in the case of lithium–pilocarpine-induced status epilepticus [ 105 ].…”