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
Role of EGFL7 in human cancers: A review

Autor(es)
de Oliveira C, - Gonçalves PG, - Bidinotto LT.

Palavras chave
angiogenesis - cancer - EGFL7 - pathways

Resumo
EGFL7 is a proangiogenic factor. It has been widely described with having a vital role in tubulogenesis and regulation of angiogenesis, mainly during embryogenesis and organogenesis. It has been mainly associated with NOTCH pathway, but there are reports showing association with MAPK and integrin pathways. Given its association with angiogenesis and these other pathways, there are several studies associating EGFL7 with carcinogenesis. In fact, most of the studies have pointed to EGFL7 as an oncogene, and some of them suggest EGFL7 expression as a possible biomarker of prognosis or use for a patients follow‐up. Here, we review the molecular pathways which EGFL7 is associated and highlight several studies describing the role of EGFL7 in tumorigenesis, separated by tumor type. Besides its role on angiogenesis, EGFL7 may act in other pathways as oncogene, which makes it a possible biomarker and a candidate to targeted therapy.

Citação
de Oliveira C, Gonçalves PG, Bidinotto LT. Role of EGFL7 in human cancers: A review. J Cell Physiol. 2023 Aug;238(8):1756-1767. doi: 10.1002/jcp.31084. Epub 2023 Jul 25. PMID: 37490307.

Data documento
07/05/2024

Título
Significance of Chr9p22.1-p21.3 Deletion in Cancer Development: A Pan-cancer In Silico Analysis

Autor(es)
Gonçalves PG, Reis RM, Bidinotto LT.

Palavras chave
locus - In silico analysis - TCGA - gene expression - prognostic value

Resumo
Background/aim: Deletions in chr9p22.1-21.3 locus have been related to the development of several types of cancer, mainly due to the presence of CDKN2A and CDKN2B genes. However, there are several other genes in the region with potential importance in tumorigenesis. We, therefore, aimed to analyze in silico the potential prognostic significance of alterations in copy number and expression of genes present in the chr9p22.1-21.3 locus in 33 TCGA datasets (approximately 10,000 patients). Materials and methods: We analyzed which of the 27 genes are expressed in the datasets. Additionally, we associated the deletion of the locus with survival (log rank analysis) and hazard ratio (HR) (univariate cox regression). Finally, we performed univariate, multivariate, and overall survival analyses in 13 datasets considering the expression of 10 genes present in the locus. Results: We identified 10 genes of the chr9p22.1-21.3 locus expressed in the datasets (MLLT3, FOCAD, PTPLAD2, KLHL9, IFNE, MTAP, CDKN2A, CDKN2B, DMRTA1 and ELAVL2). Moreover, we found that deletion in at least 1 of these genes was associated with poor survival and increased HR in 13 datasets: adrenocortical carcinoma (ACC), glioblastoma (GBM), head and neck squamous cell carcinoma (HNSC), kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), low-grade glioma (LGG), lung adenocarcinoma (LUAD), mesothelioma (MESO), pancreatic adenocarcinoma (PAAD), prostate adenocarcinoma (PRAD), rectum adenocarcinoma (READ), sarcoma (SARC) and uterine corpus endometrial carcinoma (UCEC). Finally, we found an association of survival/HR and altered expression of MLLT3 in the MESO dataset, of FOCAD in the READ dataset, of PTPLAD2 in the KIRP dataset, of KLHL9 in the LGG and UCEC datasets, of IFNE in ACC, GBM, KIRC and LUAD datasets, of MTAP in LGG, LUAD and MESO datasets, of CDKN2A in the HNSC, KIRC and MESO datasets, of CDKN2B in the LGG and READ datasets, of DMRTA1 in SARC datasets and of ELAVL2 in the LGG dataset (p<0.01 for all associations). Conclusion: Besides CDKN2A and CDKN2B, numerous other genes are possibly related to cancer development, requiring further investigation.

Citação
Gonçalves PG, Reis RM, Bidinotto LT. Significance of Chr9p22.1-p21.3 Deletion in Cancer Development: A Pan-cancer In Silico Analysis. Anticancer Res. 2022 Nov;42(11):5291-5304. doi: 10.21873/anticanres.16036. PMID: 36288884.