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
13/03/2025

Título
Implementation of the ProMisE classifier and validation of its prognostic impact in Brazilian endometrial carcinomas

Autor(es)
Andrade DAP, Bonatelli M, de Paula FE, Berardinelli GN, Teixeira GR, Dos Reis MT, Barbin FF, Andrade CEMDC, Aguiar VP, Hermoza AD, Hirai WY, Schmidt RL, Reis RM, Dos Reis R.

Palavras chave
Oncologia Ginecológica - Hospital do Amor Barretos SP

Resumo
Purpose Molecular classification of endometrial cancer (EC) has emerged as a key approach to individualize therapy and define prognostic outcomes. This study aimed to implement the traditional ProMisE classification in a Brazilian population, compared with a molecular setting of ProMisE biomarkers, and evaluate its impact on patients’ prognosis. Patient and methods A prospective cohort of 114 patients with primary EC treated at Barretos Cancer Hospital (BCH) between October 2020 and December 2022 was conducted. Pathology diagnosis, staging, treatment, and follow-up data were collected. The traditional ProMisE methodology was carried out by POLE hotspot sequencing and immunohistochemistry (IHC) for p53 and mismatch repair (MMR) proteins. We further evaluate the MMR and TP53 status by molecular approach, namely microsatellite instability (MSI) by PCR-based and TP53 mutation analysis by next-generation sequencing (NGS). The results of the 4 molecular groups in both methodologies were compared regarding agreement accuracy and survival outcomes. Results Among the 114 cases, the traditional ProMisE groups were: POLEmut 15.8%, MMRd 28.1%, p53abn 27.2%, and no specific molecular profile (NSMP) 28.9%. Considering the molecular classification approach, we observed a POLEmut group of 15.8%, MSI group of 23.7%, TP53 mutation of 27.2%, and NSMP of 33.3%. The concordance rate of both approaches was 86.8% (99/114 cases) with an overall accuracy of 0.87. Importantly, both traditional and molecular ProMisE approaches were associated with significant distinct overall survival (OS) and progression-free survival (PFS) outcomes, with POLEmut patients exhibiting a better prognosis (93.8% OS, at 24 months), whereas the p53abn having a worse survival time (68.9% of OS, at 24 months). Conclusion We reported for the first time the Brazilian profile of the ProMisE classification of endometrial cancer and demonstrated the prognostic impact of the traditional and molecular ProMisE classification on patient outcomes.