Data documento
03/05/2024

Título
EGFL7 expression profile in IDH-wildtype glioblastomas is associated with poor patient outcome

Autor(es)
da Costa BHB, - Becker AP, - Neder L, - Gonçalves PG, - de Oliveira C, - Polverini AD, - Clara CA, - Teixeira GR, - Reis RM, - Bidinotto LT.

Palavras chave
EGFL7 - Glioblastoma IDH-wildtype - Notch pathway - PI3K-Akt pathway - Rap1 pathway

Resumo
Background: Despite the advances in glioblastoma (GBM) treatment, the average life span of patients is 14 months. Therefore, it is urgent to identity biomarkers of prognosis, treatment response, or development of novel treatment strategies. We previously described the association of high epidermal growth factor-like domain multiple 7 (EGFL7) expression and unfavorable outcome of pilocytic astrocytoma patients. The present study aims to analyze the prognostic potential of EGFL7 in GBM isocitrate dehydrogenase (IDH)-wildtype, using immunohistochemistry and in silico approaches. Methods: Spearmans correlation analysis of The Cancer Genome Atlas RNA sequencing data was performed. The genes strongly correlated to EGFL7 expression were submitted to enrichment gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Additionally, EGFL7 expression was associated with patient overall survival. The expression of EGFL7 was analyzed through immunohistochemistry in 74 GBM IDH-wildtype patients samples, and was associated with clinicopathological data and overall survival. Results: In silico analysis found 78 genes strongly correlated to EGFL7 expression. These genes were enriched in 40 biological processes and eight KEGG pathways, including angiogenesis/vasculogenesis, cell adhesion, and phosphoinositide 3-kinase-Akt, Notch, and Rap1 signaling pathways. The immunostaining showed high EGFL7 expression in 39 cases (52.7%). High immunolabelling was significantly associated with low Karnofsky Performance Status and poor overall survival. Cox analysis showed that GBMs IDH-wildtype with high EGFL7 expression presented a higher risk of death compared to low expression (hazard ratio, 1.645; 95% confidence interval, 1.021 to 2.650; p = .041). Conclusions: This study gives insights regarding the genes that are correlated with EGFL7, as well as biological processes and signaling pathways, which should be further investigated in order to elucidate their role in glioblastoma biology.

Citação
da Costa BHB, Becker AP, Neder L, Gonçalves PG, de Oliveira C, Polverini AD, Clara CA, Teixeira GR, Reis RM, Bidinotto LT. EGFL7 expression profile in IDH-wildtype glioblastomas is associated with poor patient outcome. J Pathol Transl Med. 2022 Jul;56(4):205-211. doi: 10.4132/jptm.2022.04.22. Epub 2022 Jun 15. PMID: 35698739; PMCID: PMC9288890.

Data documento
02/05/2024

Título
High frequency of WNT-activated medulloblastomas with CTNNB1 wild type suggests a higher proportion of hereditary cases in a Latin-Iberian population

Autor(es)
Moreno DA - Bonatelli M - Antoniazzi AP - de Paula FE - Leal LF - Garcia FAO - de Paula AE - Teixeira GR - Santana IVV - Saggioro F - Neder L - Valera ET - Scrideli CA - Stavale J - Malheiros SMF - Lima M - Hajj GNM - Garcia-Rivello H - Christiansen S - Nunes S - Gil-da-Costa MJ - Pinheiro J - Martins FD - Junior CA - Mançano BM - Reis RM.

Resumo
Medulloblastomas are the most common primary malignant brain tumors in children. They are divided into molecular subgroups: WNT-activated, SHH-Activated, TP53 mutant or wild type, and non-WNT/non-SHH (Groups 3 and 4). WNT-activated medulloblastomas are usually caused by mutations in the CTNNB1 gene (85%–90%), and most remaining cases of CTNNB1 wild type are thought to be caused by germline mutations in APC. So far, the frequencies of CTNNB1 have been reported mainly in North American and European populations. The aim of this study was to report the frequency of CTNNB1 mutations in WNT-activated medulloblastomas in a Latin-Iberian population and correlate with their clinicopathological characteristics.

Citação
Moreno DA, Bonatelli M, Antoniazzi AP, de Paula FE, Leal LF, Garcia FAO, de Paula AE, Teixeira GR, Santana IVV, Saggioro F, Neder L, Valera ET, Scrideli CA, Stavale J, Malheiros SMF, Lima M, Hajj GNM, Garcia-Rivello H, Christiansen S, Nunes S, Gil-da-Costa MJ, Pinheiro J, Martins FD, Junior CA, Mançano BM, Reis RM. High frequency of WNT-activated medulloblastomas with CTNNB1 wild type suggests a higher proportion of hereditary cases in a Latin-Iberian population. Front Oncol. 2023 Sep 4;13:1237170. doi: 10.3389/fonc.2023.1237170. PMID: 37746264; PMCID: PMC10513896.