Cortical gene expression correlates of temporal lobe epileptogenicity

McCallum, Abigail P.; Gallek, Matthew J.; Ramey, Wyatt L.; Manziello, Ann; Witte, Marlys H.; Bernas, Michael; Labiner, David M.; Weinand, Martin E.

doi:10.1016/j.pathophys.2016.05.006

Cited by 9 publications

(5 citation statements)

References 71 publications

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“…Recent studies suggest that the stereotypical waveform similarity (Liu et al, 2018) or combination of spikes and HFOs (Roehri et al, 2017) in particular represent sensitive and specific biomarkers for delineating the epileptogenic area in the brain. McCallum et al (McCallum et al, 2016) identified 40 regulated genes that indicate epileptogenicity of the lateral temporal cortex in patients operated on due to drug-refractory TLE. (Raoof et al, 2017) reported that elevated levels of miR-451a or miR-21p, or decreased levels of miR-19b in the CSF differentiate patients with SE from controls.…”

Section: Diagnostic Biomarkers For Epileptogenesis and Epileptogenicity-mentioning

confidence: 99%

Epilepsy biomarkers – Toward etiology and pathology specificity

Pitkänen

Ndode-Ekane

Lapinlampi

et al. 2019

Neurobiology of Disease

136

131

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A biomarker is a characteristic that is measured as an indicator of normal biologic processes, pathogenic processes, or responses to an exposure or intervention, including therapeutic interventions. Biomarker modalities include molecular, histologic, radiographic, or physiologic characteristics. In 2015, the FDA-NIH Joint Leadership Council developed the BEST Resource (Biomarkers, EndpointS, and other Tools) to improve the understanding and use of biomarker terminology in biomedical research, clinical practice, and medical product development. The BEST biomarker categories include: (a) susceptibility/risk biomarkers, (b) diagnostic biomarkers, (c) monitoring biomarkers, (d) prognostic biomarkers, (e) predictive biomarkers, (f) pharmacodynamic/response biomarkers, and (g) safety biomarkers. Here we review 30 epilepsy biomarker studies that have identified (a) diagnostic biomarkers for epilepsy, epileptogenesis, epileptogenicity, drug-refractoriness, and status epilepticus - some of the epileptogenesis and epileptogenicity biomarkers can also be considered prognostic biomarkers for the development of epilepsy in subjects with a given brain insult, (b) predictive biomarkers for epilepsy surgery outcome, and (c) a response biomarker for therapy outcome. The biomarker modalities include plasma/serum/exosomal and cerebrospinal fluid molecular biomarkers, brain tissue molecular biomarkers, imaging biomarkers, electrophysiologic biomarkers, and behavioral/cognitive biomarkers. Both single and combinatory biomarkers have been described. Most of the reviewed biomarkers have an area under the curve >0.800 in receiver operating characteristics analysis, suggesting high sensitivity and specificity. As discussed in this review, we are in the early phase of the learning curve in epilepsy biomarker discovery. Many of the seven biomarker categories lack epilepsy-related biomarkers. There is a need for epilepsy biomarker discovery using proper, statistically powered study designs with validation cohorts, and the development and use of novel analytical methods. A strategic roadmap to discuss the research priorities in epilepsy biomarker discovery, regulatory issues, and optimization of the use of resources, similar to those devised in the cancer and Alzheimer's disease research areas, is also needed.

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Section: Diagnostic Biomarkers For Epileptogenesis and Epileptogenicity-mentioning

confidence: 99%

Epilepsy biomarkers – Toward etiology and pathology specificity

Pitkänen

Ndode-Ekane

Lapinlampi

et al. 2019

Neurobiology of Disease

136

131

View full text Add to dashboard Cite

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“…Another interesting relationship was observed between HGFAC expression and epilepsy. Decreased cortical HGFAC mRNA levels were correlated with increased frequency of temporal lobe epilepsy [ 59 ].…”

Section: Impaired Hgfac Function and Diseasesmentioning

confidence: 99%

Hepatocyte Growth Factor Activator: A Proteinase Linking Tissue Injury with Repair

Fukushima

Uchiyama²,

Tanaka

et al. 2018

IJMS

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Hepatocyte growth factor (HGF) promotes pleiotropic signaling through its specific receptor tyrosine kinase, MET. As such, it has important roles in the regeneration of injured tissues. Since HGF is produced mainly by mesenchymal cells and MET is expressed in most epithelial, endothelial and somatic stem cells, HGF functions as a typical paracrine growth factor. HGF is secreted as an inactive precursor (proHGF) and requires proteolytic activation to initiate HGF-induced MET signaling. HGF activator (HGFAC) is a serum activator of proHGF and produces robust HGF activities in injured tissues. HGFAC is a coagulation factor XII-like serine endopeptidase that circulates in the plasma as a zymogen (proHGFAC). Thrombin, kallikrein-related peptidase (KLK)-4 or KLK-5 efficiently activates proHGFAC. The activated HGFAC cleaves proHGF at Arg494-Val495, resulting in the formation of the active disulfide-linked heterodimer HGF. Macrophage stimulating protein, a ligand of RON, is also activated by HGFAC in vivo. Although HGFAC functions primarily at the site of damaged tissue, a recent report has suggested that activated HGFAC relays a signal to stem cells in non-injured tissues via proHGF activation in the stem cell niche. This review focuses on current knowledge regarding HGFAC-mediated proHGF activation and its roles in tissue regeneration and repair.

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“…Seizure frequency has traditionally served as a clinical measure of temporal lobe epilepsy severity (i.e. epileptogenicity) and as a quantitative measure of the TLE response to medical and surgical therapy [ 6 ]. In the emerging era of personalized medicine, the development of biomarkers may improve the quantitative assessment of the severity and response to treatment of various disease states [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Leukocyte differential gene expression prognostic value for high versus low seizure frequency in temporal lobe epilepsy

Sprissler,

Hammer,

Labiner

et al. 2024

BMC Neurol

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Background This study was performed to test the hypothesis that systemic leukocyte gene expression has prognostic value differentiating low from high seizure frequency refractory temporal lobe epilepsy (TLE). Methods A consecutive series of patients with refractory temporal lobe epilepsy was studied. Based on a median baseline seizure frequency of 2.0 seizures per month, low versus high seizure frequency was defined as ≤ 2 seizures/month and > 2 seizures/month, respectively. Systemic leukocyte gene expression was analyzed for prognostic value for TLE seizure frequency. All differentially expressed genes were analyzed, with Ingenuity® Pathway Analysis (IPA®) and Reactome, to identify leukocyte gene expression and biological pathways with prognostic value for seizure frequency. Results There were ten males and six females with a mean age of 39.4 years (range: 16 to 62 years, standard error of mean: 3.6 years). There were five patients in the high and eleven patients in the low seizure frequency cohorts, respectively. Based on a threshold of twofold change (p < 0.001, FC > 2.0, FDR < 0.05) and expression within at least two pathways from both Reactome and Ingenuity® Pathway Analysis (IPA®), 13 differentially expressed leukocyte genes were identified which were all over-expressed in the low when compared to the high seizure frequency groups, including NCF2, HMOX1, RHOB, FCGR2A, PRKCD, RAC2, TLR1, CHP1, TNFRSF1A, IFNGR1, LYN, MYD88, and CASP1. Similar analysis identified four differentially expressed genes which were all over-expressed in the high when compared to the low seizure frequency groups, including AK1, F2R, GNB5, and TYMS. Conclusions Low and high seizure frequency TLE are predicted by the respective upregulation and downregulation of specific leukocyte genes involved in canonical pathways of neuroinflammation, oxidative stress and lipid peroxidation, GABA (γ-aminobutyric acid) inhibition, and AMPA and NMDA receptor signaling. Furthermore, high seizure frequency-TLE is distinguished prognostically from low seizure frequency-TLE by differentially increased specific leukocyte gene expression involved in GABA inhibition and NMDA receptor signaling. High and low seizure frequency patients appear to represent two mechanistically different forms of temporal lobe epilepsy based on leukocyte gene expression.

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Cortical gene expression correlates of temporal lobe epileptogenicity

Cited by 9 publications

References 71 publications

Epilepsy biomarkers – Toward etiology and pathology specificity

Epilepsy biomarkers – Toward etiology and pathology specificity

Hepatocyte Growth Factor Activator: A Proteinase Linking Tissue Injury with Repair

Leukocyte differential gene expression prognostic value for high versus low seizure frequency in temporal lobe epilepsy

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