Abstract
Gliomas represent 70% of all central system nervous tumors and are classified according to the degree of malignancy as low- or high-grade. The permanent activation of the EGFR/PI3K/AKT pathway by various genetic or post-translational alterations of EGFR, PI3KCA, and PTEN has been associated with increased proliferation and resistance to apoptosis. The present study aimed to analyze the molecular/genetic changes in the EGFR/PI3K/AKT/PTEN pathway between low-grade and high-grade gliomas in a sample of Colombian patients. A total of 30 samples were tested for PI3K and PTEN mutations, EGFR, PI3K, and AKT gene amplification, AKT, PI3K, BAX, Bcl2 expression levels, and phosphorylation of AKT and PTEN, EGFR and/or PI3K gene amplification was found in 50% of low-grade and 45% of high-grade ones. AKT amplification was found in 25% of the low-grade and 13.6% of the high-grade. The expression of PI3K, AKT, Bcl2, and BAX was increased particularly to a high degree. AKT phosphorylation was found in 66% of low-grade and 31.8% of high-grade. Increased phosphorylation of PTEN was found in 77% low-grade and 66% high-grade. Our results indicate that alterations in the EGFR/PI3K/AKT/PTEN pathway could be important in the initiation and malignant progression of this type of tumor.
Highlights
Accepted: 14 December 2021Gliomas are a heterogeneous group of central nervous system (CNS) tumors
I and grade II astrocytoma, which represents an astrocytic tumor, grade III astrocytoma, which consists of an anaplastic tumor, and grade IV astrocytoma); Grade IV is a lethal form of brain cancer that affects adults with poor prognoses
Our results demonstrate the differential regulation of the phosphatidylinositol 3 kinase (PI3K)/AKT/PTEN pathway in high- and low-grade gliomas, which could be of great importance for diagnosing and treating these types of tumors
Summary
Gliomas are a heterogeneous group of central nervous system (CNS) tumors. According to the expression of specific markers, it is possible to distinguish subtypes of proneural, neural, mesenchymal, or classical GBM [1,2,3]. New ways of classifying have been proposed, including the classic, proneural, and mesenchymal types, since the neural subtype consists of non-tumor cells [4], 2021 WHO classification better describes the differences between gliomas of adults and pediatrics. The microenvironment plays an important role in the evolution of this type of tumor, towards different functional states that determine the heterogeneity, largely influenced by cellular metabolism, bioenergetic fitness, availability of nutrients, proximity to blood vessels, biochemical gradients, regulation of oxidative phosphorylation (OXPHOS), glycolysis and the response to hypoxia [7] In glioblastoma, pituitary adenylate cyclase-activating polypeptide (PACAP)
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