Identification of serum miRNAs differentially expressed in human epilepsy at seizure onset and post-seizure

Sun, Jijun; Cheng, Wan-Jung; Liu, Lifeng; Tao, Shuxin; Xia, Zhangyong; Qi, Lifeng; Huang, Min

doi:10.3892/mmr.2016.5906

Cited by 25 publications

(19 citation statements)

References 37 publications

(36 reference statements)

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“…Moreover, 10 miRNAs remained regulated for up to 20-28 h in a subgroup of patients that experienced a seizure during sleep. miRNA regulation was also reported by Sun et al (Sun et al, 2016a), who found a correlation between seizure frequency and miR-30a regulation. Although seizure frequency did not affect the plasma miRNA levels in a study with drug-refractory patients (Avansini et al, 2017), the timing of seizure occurrence relative to tissue sampling can be a confounding factor in the analysis and should be monitored and reported in epilepsy biomarker studies.…”

Section: Subject-related Informationsupporting

confidence: 58%

Epilepsy biomarkers – Toward etiology and pathology specificity

Pitkänen

Ndode-Ekane

Lapinlampi

et al. 2019

Neurobiology of Disease

130

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: Subject-related Informationsupporting

confidence: 58%

Epilepsy biomarkers – Toward etiology and pathology specificity

Pitkänen

Ndode-Ekane

Lapinlampi

et al. 2019

Neurobiology of Disease

130

131

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“…To our knowledge there are only four reports investigating serum levels of microRNAs in patients with epilepsy as compared to healthy controls [12–15]. Given the great heterogeneity of epilepsy syndromes it becomes clear that additional studies are urgently needed.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA hsa-miR-134 is a circulating biomarker for mesial temporal lobe epilepsy

et al. 2017

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Epilepsy is misdiagnosed in up to 25% of patients, leading to serious and long-lasting consequences. Recently, circulating microRNAs have emerged as potential biomarkers in a number of clinical scenarios. The purpose of this study was to identify and to validate circulating microRNAs that could be used as biomarkers in the diagnosis of epilepsy. Quantitative real-time PCR was used to measure plasma levels of three candidate microRNAs in two phases of study: an initial discovery phase with 14 patients with mesial temporal lobe epilepsy (MTLE), 13 with focal cortical dysplasia (FCD) and 16 controls; and a validation cohort constituted of an independent cohort of 65 patients with MTLE and 83 controls. We found hsa-miR-134 downregulated in patients with MTLE (p = 0.018) but not in patients with FCD, when compared to controls. Furthermore, hsa-miR-134 expression could be used to discriminate MTLE patients with an area under the curve (AUC) of 0.75. To further assess the robustness of hsa-miR-134 as a biomarker for MTLE, we studied an independent cohort of 65 patients with MTLE, 27 of whom MTLE patients were responsive to pharmacotherapy, and 38 patients were pharmacoresistant and 83 controls. We confirmed that hsa-miR-134 was significantly downregulated in the plasma of patients with MTLE when compared with controls (p < 0.001). In addition, hsa-miR-134 identified patients with MTLE regardless of their response to pharmacotherapy or the presence of MRI signs of hippocampal sclerosis. We revealed that decreased expression of hsa-miR-134 could be a potential non-invasive biomarker to support the diagnosis of patients with MTLE.

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“…We performed a manual literature search in PubMed and the Human MicroRNA Disease Database (HMDD; v3.2) with the combined keywords “FCD, seizures, epilepsy or status epilepticus” and the four upregulated miRNAs (miR-194-2, miR-15a, miR-132, and miR-145), to confirm the relationship between the miRNAs and FCD or different types of seizures and epilepsy [ 52 ] ( Table 2 ). According to the reported literature in PubMed, these miRNAs related to FCD and different forms of seizures and epilepsy [ 30 , 31 , 53 , 54 , 55 , 56 , 57 ] were identified, including the reported evidence of diagnostic and prognostic biomarkers and therapeutic targets ( Table 2 ). Each single miRNA can influence multiple genes.…”

Section: Resultsmentioning

confidence: 99%

Circulating MicroRNAs from Serum Exosomes May Serve as a Putative Biomarker in the Diagnosis and Treatment of Patients with Focal Cortical Dysplasia

Chen

Pan

Huang

et al. 2020

Cells

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Focal cortical dysplasia (FCD) is a congenital malformation of cortical development where the cortical neurons located in the brain area fail to migrate in the proper formation. Epilepsy, particularly medically refractory epilepsy, is the most common clinical presentation for all types of FCD. This study aimed to explore the expression change of circulating miRNAs in patients with FCD from serum exosomes. A total of nine patients with FCD and four healthy volunteers were enrolled in this study. The serum exosomes were isolated from the peripheral blood of the subjects. Transmission electron microscopy (TEM) was used to identify the exosomes. Both exosomal markers and neuronal markers were detected by Western blotting analysis to prove that we could obtain central nervous system-derived exosomes from the circulation. The expression profiles of circulating exosomal miRNAs were assessed using next-generation sequencing analysis (NGS). We obtained a total of 107 miRNAs with dominant fold change (>2-fold) from both the annotated 5p-arm and 3p-arm of 2780 mature miRNAs. Based on the integrated platform of HMDD v3.2, miRway DB and DIANA-miRPath v3.0 online tools, and confirmed by MiRBase analysis, four potentially predicted miRNAs from serum exosomes in patients with FCD were identified, including miR194-2-5p, miR15a-5p, miR-132-3p, and miR-145-5p. All four miRNAs presented upregulated expression in patients with FCD compared with controls. Through Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and pathway category of four target miRNAs, we found eight possible signaling pathways that may be related to FCD. Among them, we suggest that the mTOR signaling pathway, PI3K-Akt signaling pathway, p53 signaling pathway, and cell cycle regulation and TGF-beta signaling pathway are high-risk pathways that play a crucial role in the pathogenesis of FCD and refractory epilepsy. Our results suggest that the circulating miRNAs from exosomes may provide a potential biomarker for diagnostic, prognostic, and therapeutic adjuncts in patients with FCD and refractory epilepsy.

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Identification of serum miRNAs differentially expressed in human epilepsy at seizure onset and post-seizure

Cited by 25 publications

References 37 publications

Epilepsy biomarkers – Toward etiology and pathology specificity

Epilepsy biomarkers – Toward etiology and pathology specificity

MicroRNA hsa-miR-134 is a circulating biomarker for mesial temporal lobe epilepsy

Circulating MicroRNAs from Serum Exosomes May Serve as a Putative Biomarker in the Diagnosis and Treatment of Patients with Focal Cortical Dysplasia

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