Serum Exosomal Proteins F9 and TSP-1 as Potential Diagnostic Biomarkers for Newly Diagnosed Epilepsy.

Zijun Lin,Meiling Wang,Fei Xiao,Junhong Ma,Yixue Gu,Yi Guo,Xuefeng Wang,Yuanyuan Chen,Ruijiao Zhou,Xin Tian

doi:10.3389/fnins.2020.00737

Abstract

Epilepsy is one of the most common chronic neurological diseases in the world, with a high incidence, a high risk of sudden unexplained death, and diagnostic challenges. Exosomes are nanosized extracellular vesicles that are released into physical environments and carry a variety of biological information. Moreover, exosomes can also be synthesized and released from brain cells, passing through the blood-brain barrier, and can be detected in peripheral blood or cerebrospinal fluid. Our study using the tandem mass tag (TMT) approach showed that a total of 76 proteins were differentially expressed in serum exosomes between epilepsy patients and healthy controls, with 6 proteins increasing and 70 proteins decreasing. Analysis of large clinical samples and two mouse models of chronic epilepsy indicated that two significantly differentially expressed serum exosomal proteins, coagulation factor IX (F9) and thrombospondin-1 (TSP-1), represent promising biomarkers for the diagnosis of epilepsy, with area under the curve (AUC) values of up to 0.7776 (95% CI, 0.7306–0.8246) and 0.8534 (95% CI, 0.8152–0.8916), respectively. This is the first study of exosomal proteins in epilepsy, and it suggests that exosomes are promising new tools for the diagnosis of epilepsy.

Highlights

Epilepsy is one of the most common chronic neurological diseases in the world, and it affects people of all ages, without geographic, social or ethnic boundaries
The results showed that the expression of F9 in serum exosomes from epilepsy patients was higher than that in serum exosomes from healthy controls (∗∗∗∗P < 0.0001, Figure 5Aa) and that the expression of TSP-1 in serum exosomes from epilepsy patients was lower than that in serum exosomes from healthy controls These data indicate that serum exosomal proteins are reliable
We verified the expression levels of these three proteins in serum exosomes, and the results showed that only F9 and TSP-1 were significantly different, which was consistent with the results of tandem mass tag (TMT) proteomic analysis

Summary

Introduction

Epilepsy is one of the most common chronic neurological diseases in the world, and it affects people of all ages, without geographic, social or ethnic boundaries. The risk of premature death in epilepsy patients is significantly higher than that in the general population (Nevalainen et al, 2014). There are 180,000 epilepsyrelated deaths worldwide each year (Lozano et al, 2012). Sudden unexplained death in epilepsy (SUDEP), which will soon become the second most common cause of decline in adult life years after stroke, accounts for an estimated 1.16 deaths per 1,000 epilepsy patients (Thurman et al, 2014). Drugs are the main treatment for epilepsy. There is literature showing that early antiepileptic drug (AED) treatment effectively reduces the risk of recurrence of seizures in the short

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Conclusion