Identification of serum miR-378 and miR-575 as diagnostic indicators and predicting surgical prognosis in human epilepsy

  • XiuXiu Li Linyi Central Hospital
  • ZhiQing Gao Linyi Central Hospital
  • Mei Ling Ma Linyi Central Hospital
  • Li Li Linyi Central Hospital
  • ShiFeng Guo Linyi Central Hospital
Keywords: miR-378, miR-575, human epilepsy, serum biomarkers

Abstract


Objectives: Epilepsy (EP) was a common neurological disorder characterized by excessive abnormal synchronization of neuronal discharges in the brain due to chronic recurrent seizures of multiple etiologies. Recently, a variety of miRNAs were found to be dysregulated,  participating in the occurrence and development of various diseases, including EP. This study mainly determines the abnormal expression of miR-378 and miR-575 in EP patients to validate their potential in distinguishing EP from healthy controls.

Methods: Clinical parameters in all participants were recorded. qRT-PCR analysis was applied to determine the expressions of miR-378 and miR-575 in EP patients and healthy volunteers. The student’s t-test and chi-square test was applied to analyze clinical indicators between EP patients and controls. According to the surgical outcome, EP patients were further divided into Engel I~IV EP. The potentials of miR-378 and miR-575 in discriminating EP from healthy participants and predicting surgical prognosis were calculated by receiver operating characteristic (ROC) analysis.

Results: There were no significant differences in age, gender, smoking history, and BMI index between EP patients and healthy controls. miR-378 and miR-575 were significantly declined in Engel I~II and III~IV EP patients in comparison to healthy participants. Moreover, miR-378 and miR-575 displayed high sensitivity, specificity, and accuracy in discriminating EP patients from healthy controls and predicting surgical outcome. Moreover, after surgical treatment, miR-378 and miR-575 levels were increased compared with those at admission, suggesting their potentials in treatment response.

Conclusion: miR-378 and miR-575 could be utilized as novel and non-invasive serum biomarkers in discriminating EP from healthy controls and predicting surgical outcome, shedding new insights on epileptogenesis and EP treatment.

 

References

1. Beghi, E., Giussani, G. & Sander, J.W. The natural history and prognosis of epilepsy. Epileptic Disord 17, 243-53 (2015). PMID: 26234761.
2. Boison, D. & Steinhäuser, C. Epilepsy and astrocyte energy metabolism. Glia 66, 1235-1243 (2018). PMID: 29044647.
3. Cheng Y, Mai Q, Zeng X, et al. Propionate relieves pentylenetetrazol-induced seizures, consequent mitochondrial disruption, neuron necrosis and neurological deficits in mice. Biochem Pharmacol 169, 113607 (2019). PMID: 31491413.
4. Li, W., Hao, N., Xiao, Y. & Zhou, D. Clinical characteristics and pregnancy outcomes of new onset epilepsy during pregnancy. Medicine (Baltimore) 98, e16156 (2019). PMID: 31277117.
5. Symonds JD, Zuberi SM, Stewart K, et al. Incidence and phenotypes of childhood-onset genetic epilepsies: a prospective population-based national cohort. Brain 142, 2303-2318 (2019). PMID: 31302675.
6. Zijlmans, M., Zweiphenning, W. & van Klink, N. Changing concepts in presurgical assessment for epilepsy surgery. Nat Rev Neurol 15, 594-606 (2019). PMID: 31341275.
7. Supriya, S., Siuly, S., Wang, H. & Zhang, Y. Epilepsy Detection from EEG using Complex Network Techniques: A Review. IEEE Rev Biomed Eng Pp(2021). PMID: 33523816.
8. Ghafouri-Fard, S., Shoorei, H., Taheri, M. & Sanak, M. Emerging role of non-coding RNAs in allergic disorders. Biomed Pharmacother 130, 110615 (2020). PMID: 32777705.
9. Jonas, S. & Izaurralde, E. Towards a molecular understanding of microRNA-mediated gene silencing. Nat Rev Genet 16, 421-33 (2015). PMID: 26077373.
10. Wang J, Zhang C, Peng X, et al. A combination of four serum miRNAs for screening of lung adenocarcinoma. Hum Cell 33, 830-838 (2020). PMID: 32388809.
11. Condrat CE, Thompson DC, Barbu MG, et al. miRNAs as Biomarkers in Disease: Latest Findings Regarding Their Role in Diagnosis and Prognosis. Cells 9(2020). PMID: 31979244.
12. Ma, Y. The Challenge of microRNA as a Biomarker of Epilepsy. Curr Neuropharmacol 16, 37-42 (2018). PMID: 28676013.
13. Wang J, Yu JT, Tan L, et al. Genome-wide circulating microRNA expression profiling indicates biomarkers for epilepsy. Sci Rep 5, 9522 (2015). PMID: 25825351.
14. Huang, W.S. & Zhu, L. MiR-134 expression and changes in inflammatory cytokines of rats with epileptic seizures. Eur Rev Med Pharmacol Sci 22, 3479-3484 (2018). PMID: 29917202.
15. Zhang, X., Li, X., Li, B., Sun, C. & Zhang, P. miR-21-5p protects hippocampal neurons of epileptic rats via inhibiting STAT3 expression. Adv Clin Exp Med 29, 793-801 (2020). PMID: 32745381.
16. Cattani AA, Allene C, Seifert V, et al. Involvement of microRNAs in epileptogenesis. Epilepsia 57, 1015-26 (2016). PMID: 27207608.
17. Henshall DC, Hamer HM, Pasterkamp RJ, et al. MicroRNAs in epilepsy: pathophysiology and clinical utility. Lancet Neurol 15, 1368-1376 (2016). PMID: 27839653.
18. Sun J, Cheng W, Liu L, et al. Identification of serum miRNAs differentially expressed in human epilepsy at seizure onset and post-seizure. Mol Med Rep 14, 5318-5324 (2016). PMID: 27840934.
19. Thijs, R.D., Surges, R., O'Brien, T.J. & Sander, J.W. Epilepsy in adults. Lancet 393, 689-701 (2019). PMID: 30686584.
20. Song P, Liu Y, Yu X, et al. Prevalence of epilepsy in China between 1990 and 2015: A systematic review and meta-analysis. J Glob Health 7, 020706 (2017). PMID: 29302325
21. Zhao R, Xue P, Zhou Y, et al. Application of Robot-Assisted Frameless Stereoelectroencephalography Based on Multimodal Image Guidance in Pediatric Refractory Epilepsy: Experience of a Pediatric Center in a Developing Country. World Neurosurg 140, e161-e168 (2020). PMID: 32389862.
22. Padmanaban, V., Inati, S., Ksendzovsky, A. & Zaghloul, K. Clinical advances in photosensitive epilepsy. Brain Res 1703, 18-25 (2019). PMID: 30076791.
23. Wijnen BFM, van Mastrigt G, Evers S, et al. A systematic review of economic evaluations of treatments for patients with epilepsy. Epilepsia 58, 706-726 (2017). PMID: 28098939.
24. Nolan, S.J., Tudur Smith, C., Weston, J. & Marson, A.G. Lamotrigine versus carbamazepine monotherapy for epilepsy: an individual participant data review. Cochrane Database Syst Rev 11, Cd001031 (2016). PMID: 27841445.
25. Franco, D., Aranega, A. & Dominguez, J.N. Non-coding RNAs and Atrial Fibrillation. Adv Exp Med Biol 1229, 311-325 (2020). PMID: 32285421.
26. Vezzani A, Fujinami RS, White HS, et al. Infections, inflammation and epilepsy. Acta Neuropathol 131, 211-234 (2016). PMID: 26423537
27. Henshall, D.C. & Simon, R.P. Epilepsy and apoptosis pathways. J Cereb Blood Flow Metab 25, 1557-72 (2005). PMID: 15889042.
28. Jimenez-Mateos, E.M. & Henshall, D.C. Epilepsy and microRNA. Neuroscience 238, 218-29 (2013). PMID: 23485811.
29. Henshall, D.C. MicroRNA and epilepsy: profiling, functions and potential clinical applications. Curr Opin Neurol 27, 199-205 (2014). PMID: 24553459.
30. Wang W, Wang X, Chen L, et al. The microRNA miR-124 suppresses seizure activity and regulates CREB1 activity. Expert Rev Mol Med 18, e4 (2016). PMID: 26996991.
31. Choi, S.W., Lee, J.Y. & Kang, K.S. miRNAs in stem cell aging and age-related disease. Mech Ageing Dev 168, 20-29 (2017). PMID: 28847486.
32. Wei H, Xu Y, Chen Q, et al. Mesenchymal stem cell-derived exosomal miR-223 regulates neuronal cell apoptosis. Cell Death Dis 11, 290 (2020). PMID: 32341353.
33. Ye, Y., Xu, H., Su, X. & He, X. Role of MicroRNA in Governing Synaptic Plasticity. Neural Plast 2016, 4959523 (2016). PMID: 27034846.
34. Wang X, Zhou Y, Gao Q, et al. The Role of Exosomal microRNAs and Oxidative Stress in Neurodegenerative Diseases. Oxid Med Cell Longev 2020, 3232869 (2020). PMID: 33193999.
35. Galardi A, Colletti M, Businaro P, et al. MicroRNAs in Neuroblastoma: Biomarkers with Therapeutic Potential. Curr Med Chem 25, 584-600 (2018). PMID: 28971761.
36. Sueri C, Gasparini S, Balestrini S, et al. Diagnostic Biomarkers of Epilepsy. Curr Pharm Biotechnol 19, 440-450 (2018). PMID: 30003857.
Published
2021/11/03
Section
Original paper