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

Abstract

Diffuse gliomas are a heterogeneous group of tumors with aggressive biological behavior and a lack of effective treatment methods. Despite new molecular findings, the differences between pathohistological types still require better understanding. In this in silico analysis, we investigated AKT1, AKT2, AKT3, CHUK, GSK3β, EGFR, PTEN, and PIK3AP1 as participants of EGFR-PI3K-AKT-mTOR signaling using data from the publicly available cBioPortal platform. Integrative large-scale analyses investigated changes in copy number aberrations (CNA), methylation, mRNA transcription and protein expression within 751 samples of diffuse astrocytomas, anaplastic astrocytomas and glioblastomas. The study showed a significant percentage of CNA in PTEN (76%), PIK3AP1 and CHUK (75% each), EGFR (74%), AKT2 (39%), AKT1 (32%), AKT3 (19%) and GSK3β (18%) in the total sample. Comprehensive statistical analyses show how genomics and epigenomics affect the expression of examined genes differently across various pathohistological types and grades, suggesting that genes AKT3, CHUK and PTEN behave like tumor suppressors, while AKT1, AKT2, EGFR, and PIK3AP1 show oncogenic behavior and are involved in enhanced activity of the EGFR-PI3K-AKT-mTOR signaling pathway. Our findings contribute to the knowledge of the molecular differences between pathohistological types and ultimately offer the possibility of new treatment targets and personalized therapies in patients with diffuse gliomas.

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

“…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.…”

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

“…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.…”

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

“…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.…”