Searching for blood-based biomarkers in the epilepsies

Author(s)

Mariana Martin

• Document type: Master's Dissertation
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas
• Defense date: 2019-07-29

Examining board members

Íscia Teresinha Lopes Cendes; Clarissa Lin Yasuda; Luiz Henrique Martins Castro

• Advisor: Íscia Teresinha Lopes Cendes; Simoni Helena Avansini

Abstract

MicroRNAs are potential biomarkers due to their stability in body fluids, such as plasma and serum, and their association with diagnosis and staging of various diseases. In epilepsy, it is still a challenge to identify microRNAs that improve the diagnosis of the disease and the prediction of drug treatment. It is estimated that an incorrect diagnosis occurs in about 25% of patients with epilepsy and resistance to treatment with antiepileptic drugs can reach 30% of the cases. Thus, the objectives of this study were i) to investigate whether circulating microRNAs can be used as biomarkers in the diagnosis of specific types of epilepsy; ii) evaluate whether circulating microRNAs can be used as biomarkers of response to pharmacological treatment in epilepsy. We analyzed the expression levels of microRNAs in blood plasma in different types of epilepsy, including 14 patients with mesial temporal lobe epilepsy, seven patients with focal cortical dysplasia type II, seven with generalized genetics epilepsy and seven controls using high performance sequencing of microRNAs with HiSeq2500 - Illumina Platform. Our results indicated a total of 17 circulating microRNAs were differentially expressed (p-value, <0.01) which 11 microRNAs were found up-regulated (hsa-miR-148-3p, hsa-miR-215-5p, hsa-miR-128-3p, hsa-miR-182-5p, hsa-miR-627-5p, hsa-miR-502-3p, hsa-miR-32-5p, hsa-miR-96-5p, hsa-miR-4508, hsa-miR-636, hsa-miR-141-3p) and six microRNAs were down-regulated in patients with epilepsy (hsa-miR-330-3p, hsa-miR-877-5p, hsa-miR-139-5p, hsa-miR-4435 e hsa-miR-101-5p). Thirteen microRNAs were related to type-specific of epilepsy, three microRNAs were found common in four different types of epilepsy (hsa-miR-96-5p, hsa-miR-425-3p e hsa-miR-4508) and one microRNA was found differentially expressed when comparing responsive and resistant patients to pharmacological treatment - hsa-miR-101-5p. In conclusion, we demonstrated that it is possible to identify microRNAs differentially expressed in different types of epilepsy. In addition, we have identified microRNAs differentially expressed in plasma of patients according to the response to drug treatment. Therefore, our results may be helpful in the diagnosis and management of patients with different types of epilepsy (AU)

• FAPESP's process: 16/26172-0 - Searching for blood-based biomarkers to improve the current epilepsy diagnosis
• Grantee: Mariana Martin
• Support Opportunities: Scholarships in Brazil - Master