Dados do Trabalho

Título

Molecular signatures related to WNT pathway in dysplastic tissue and adjacent to the main dysplastic lesion in Focal Cortical Dysplasia

Introdução

Focal Cortical Dysplasia (FCD) is a malformation of cortical development characterized by abnormalities in the cerebral cortex, which results from alterations in cellular migration and differentiation processes during neurodevelopment. The WNT/β-catenin is also a signaling pathway crucial for controlling embryonic development through regulation of cellular differentiation, migration, proliferation and apoptosis. Since β-catenin is a protein responsible for cell-cell adhesion and a component of the cadherin protein complex, the WNT pathway may also be involved in the etiology of FCD.

Objetivo

Considering that the FCD’s exact etiology remains unknow, we explored genes related to WNT pathway with similar expressions between dysplastic tissue and adjacent to the main dysplastic lesion from patients with FCD.

Método

Relative gene expression was done by qRT-PCR analysis from an array containing 92 primers related to WNT pathway genes from a total of two patients with FCD type II. Expression values were obtained through the dCT method and results were analyzed in R/R studio for the generation of heatmaps.

Resultados

The gene PORCN, in patient 1, and the genes DKK1, FRZB, GSK3A, TLE6, WNT10B, WNT2, WNT5A, WNT7B, WNT8A and WNT9B, in patient 2, presented high levels expressions in both tissues, dysplastic tissue and the tissue adjacent to the main dysplastic lesion. These findings show that the "healthy" tissue, represented by the tissue adjacent to the lesion, shares molecular similarities with the dysplastic tissue, also presenting a level of alteration in its expression that can be verified through a molecular tool.

Conclusão

In conclusion, this study shows important results from WNT pathway genes related to dysplastic tissue in FCD, as it has elucidated those genes that have similar levels of expression in dysplastic tissue comparing to the tissue adjacent to the lesion. The findings are extremely important, once it allows to show at the molecular level something that the anatomo-pathological might not. These genes with common expression may explain refractoriness that this patient may have again in 6 months after surgery, highlighting that many diseases can have their responses at the molecular level.

Palavras-chave

Focal Cortical Dysplasia type II; WNT pathway; dysplastic brain tissue.