Integrative cBioPortal Analysis Revealed Molecular Mechanisms That Regulate EGFR-PI3K-AKT-mTOR Pathway in Diffuse Gliomas of the Brain

Brlek, Petar; Kafka, Anja; Bukovac, Anja; Pećina‐Šlaus, Nives

doi:10.3390/cancers13133247

Cited by 21 publications

(17 citation statements)

References 48 publications

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“…We found amplification of EGFR (12.5% in low-grade and 31.8% in high-grade gliomas: 7.7% in GBM), PI3K (50% and 45% of low- and high-grade gliomas, respectively) and AKT (25% in low-grade and 13,6% in high-grade gliomas). Previous studies have demonstrated either a trend similar to the present results [ 25 , 26 , 27 , 28 , 29 ] or the absence of amplification [ 22 , 30 , 31 ]. These contradictory results may arise from differences in the techniques used to evaluate the amplification status, as some have used FISH analysis, while others, such as ours, used RT-PCR.…”

Section: Discussionsupporting

confidence: 90%

Differential Regulation of the EGFR/PI3K/AKT/PTEN Pathway between Low- and High-Grade Gliomas

et al. 2021

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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.

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Section: Discussionsupporting

confidence: 90%

Differential Regulation of the EGFR/PI3K/AKT/PTEN Pathway between Low- and High-Grade Gliomas

et al. 2021

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“…We downloaded clinical metadata and RNA sequencing (RNAseq)-based mRNA expression data for 41 pediatric DMG patients (mean age at diagnosis in months = 7.02 ± 0.44; median = 6; range = 2–14) and 116 pediatric GBM patients (mean age at diagnosis in months = 60.01 ± 1.24; median = 60.4; range = 21–89.3) regarding TGFB isoforms TGFB1, TGFB2, and TGFB3 from the genomic data set repository stored in the cBioPortal for Cancer Genomics ( (accessed on 4 November 2022)) using the interactive web interface with full filtering functionality provided by the portal [ 41 , 42 ]. By utilizing the cBioPortal database and an archived dataset that was compiled from harmonized and annotated across multiple data consortiums, such as the open Pediatric Brain Tumor Atlas (PBTA) Project (Project ID = openpbta) and the Pacific Pediatric Neuro-Oncology Consortium Clinical Genomics Atlas (Project ID = pbta_pnoc) [ 10 , 43 , 44 , 45 ], we examined the effect of TGFB2 mRNA expression levels on PFS and OS outcomes.…”

Section: Methodsmentioning

confidence: 99%

High Intra-Tumor Transforming Growth Factor Beta 2 Level as a Predictor of Poor Treatment Outcomes in Pediatric Diffuse Intrinsic Pontine Glioma

Uckun¹,

Qazi²,

Trieu³

2023

Cancers

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Here, we report that tumor samples from newly diagnosed pediatric diffuse intrinsic pontine glioma (DIPG) patients express significantly higher levels of transforming growth factor beta 2 (TGFB2) messenger ribonucleic acid (mRNA) than control pons samples, which correlated with augmented expression of transcription factors that upregulate TGFB2 gene expression. Our study also demonstrated that RNA sequencing (RNAseq)-based high TGFB2 mRNA level is an indicator of poor prognosis for DIPG patients, but not for pediatric glioblastoma (GBM) patients or pediatric diffuse midline glioma (DMG) patients with tumor locations outside of the pons/brainstem. Notably, DIPG patients with high levels of TGFB2 mRNA expression in their tumor samples had significantly worse overall survival (OS) and progression-free survival (PFS). By comparison, high levels of transforming growth factor beta 3 (TGFB3) mRNA expression in tumor samples was associated with significantly better survival outcomes of DIPG patients, whereas high levels of transforming growth factor beta 1 (TGFB1) expression was not prognostic. Our study fills a significant gap in our understanding of the clinical significance of high TGFB2 expression in pediatric high-grade gliomas.

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“…The cBioPortal for cancer genomics is an open online resource for the interactive exploration of a wide range of cancer genomics databases. The cBioPortal significantly reduces access barriers between complex genomic data and cancer researchers, facilitating rapid, intuitive, and high-quality access to molecular profiles and the clinical prognostic relevance of large-scale cancer genomics projects [ 22 ]. We selected 12 LUAD datasets for further analysis.…”

Section: Methodsmentioning

confidence: 99%

Cystatin SN promotes epithelial-mesenchymal transition and serves as a prognostic biomarker in lung adenocarcinoma

Yang

Luo

et al. 2022

BMC Cancer

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Background Cystatins are a class of proteins that can inhibit cysteine protease and are widely distributed in human bodily fluids and secretions. Cystatin SN (CST1), a member of the CST superfamily, is abnormally expressed in a variety of tumors. However, its effect on the occurrence and development of lung adenocarcinoma (LUAD) remains unclear. Methods We obtained transcriptome analysis data of CST1 from The Cancer Genome Atlas (TCGA) and GSE31210 databases. The association of CST1 expression with prognosis, gene mutations and tumor immune microenvironment was analyzed using public databases. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were performed to investigate the potential mechanisms of CST1. Results In this study, we found that CST1 was highly expressed in lung adenocarcinoma and was associated with prognosis and tumor immune microenvironment. Genetic mutations of CST1 were shown to be related to disease-free survival (DFS) by using the c-BioPortal tool. Potential proteins binding to CST1 were identified by constructing a protein-protein interaction (PPI) network. Gene set enrichment analysis (GSEA) of CST1 revealed that CST1 was notably enriched in epithelial-mesenchymal transition (EMT). Cell experiments confirmed that overexpression of CST1 promoted lung adenocarcinoma cells migration and invasion, while knockdown of CST1 significantly inhibited lung adenocarcinoma cells migration and invasion. Conclusions Our comprehensive bioinformatics analyses revealed that CST1 may be a novel prognostic biomarker in LUAD. Experiments confirmed that CST1 promotes epithelial-mesenchymal transition in LUAD cells. These findings will help to better understand the distinct role of CST1 in LUAD.

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Integrative cBioPortal Analysis Revealed Molecular Mechanisms That Regulate EGFR-PI3K-AKT-mTOR Pathway in Diffuse Gliomas of the Brain

Cited by 21 publications

References 48 publications

Differential Regulation of the EGFR/PI3K/AKT/PTEN Pathway between Low- and High-Grade Gliomas

Differential Regulation of the EGFR/PI3K/AKT/PTEN Pathway between Low- and High-Grade Gliomas

High Intra-Tumor Transforming Growth Factor Beta 2 Level as a Predictor of Poor Treatment Outcomes in Pediatric Diffuse Intrinsic Pontine Glioma

Cystatin SN promotes epithelial-mesenchymal transition and serves as a prognostic biomarker in lung adenocarcinoma

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