Dados do Trabalho

Título

Circulating cell-free DNA as a biomarker of pharmacoresistant mesial temporal lobe epilepsy: a proof of concept

Introdução

Mesial temporal lobe epilepsy (MTLE) is a common type of pharmacoresistant epilepsy. Patients with MTLE who do not respond to treatment with antiseizure medication (ASM) may be eligible for epilepsy surgery. However, a surgical referral may be delayed by the current lack of biomarkers of pharmacoresistance in these patients. Cell-free DNA, used as liquid biopsy, has been investigated as biomarkers in several disorders, mainly cancer, and has shown to be an attractive source of information for the diagnosis, establishment of prognosis, and guide to treatment.

Objetivo

In this work, we aim to investigate the feasibility of using cfDNA from patients’ blood samples as a biomarker for medically refractory MTLE.

Método

We isolated and quantified different sources of cfDNA, mainly nuclear (nu-cfDNA) and mitochondrial cfDNA (mt-cfDNA), obtained from the plasma of 149 patients with MTLE: 49 responders and 100 patients refractory to treatment with ASM. We compared these with 80 samples from control subjects without epilepsy. We used state-of-the-art technology, including fluorescence spectrophotometry, high-resolution electrophoresis, and digital droplet PCR.

Resultados

Our results showed that the levels of mt-cfDNA can reliably discriminate patients from controls (p = 0.009). Most interestingly, levels of nu-cfDNA could reliably identify patients who are refractory to ASM compared to responders (p = 0.017). Furthermore, we found that mt-cfDNA has a specificity of 76% and nu-cfDNA has a sensitivity of 71% to identify patients with pharmacoresistant MTLE. We report here the results of the first study to show the viability of using cfDNA as biomarkers of MTLE and, most importantly, of pharmacoresistant MTLE.

Conclusão

In conclusion, we have shown that assessing circulating cfDNA levels from different sources may assist in the early diagnosis of patients with pharmacoresistant MTLE, thus helping clinicians achieve timely decision-making regarding the optimal treatment for patients with medically refractory MTLE.

Palavras-chave

Mesial temporal lobe epilepsy, cell-free DNA, non-invasive biomarker, pharmacoresistant MTLE