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 <i>AKT1</i>, <i>AKT2</i>, <i>AKT3</i>, <i>CHUK</i>, <i>GSK3β</i>, <i>EGFR</i>, <i>PTEN</i>, and <i>PIK3AP1</i> 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 <i>PTEN</i> (76%), <i>PIK3AP1</i> and <i>CHUK</i> (75% each), <i>EGFR</i> (74%), <i>AKT2</i> (39%), <i>AKT1</i> (32%), <i>AKT3</i> (19%) and <i>GSK3β</i> (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 <i>AKT3</i>, <i>CHUK</i> and <i>PTEN</i> behave like tumor suppressors, while <i>AKT1</i>, <i>AKT2</i>, <i>EGFR</i>, and <i>PIK3AP1</i> 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.