Glioblastoma is an aggressive malignant tumor of the brain and spinal cord. Due to the blood-brain barrier, the accessibility of its treatments still remains significantly challenging. Unfortunately, the recurrence rates of glioblastoma upon surgery are very high too. Hence, understanding the molecular drivers of disease progression is valuable. In this study, we aimed to investigate the molecular drivers responsible for glioblastoma progression and identify valid biomarkers. Three microarray expression profiles GSE90604, GSE50601, and GSE134470 containing healthy and glioblastoma-affected samples revealed overlapping differentially expressed genes (DEGs). The interrelational pathway enrichment analysis elucidated the halt of cell cycle checkpoints and activation of signaling pathways and led to the identification of 6 predominant hub genes. Validation of hub genes in comparison with The Cancer Genome Atlas datasets identified the potential biomarkers of glioblastoma. The study evaluated two significantly upregulated genes, (secreted protein acidic and rich in cysteine) and (vimentin) for glioblastoma. The genes (calcium voltage-gated channel subunit alpha1 e), (SH3 domain-containing like 2, endophilin A1), and (dendrin) were identified as under-expressed genes as compared to the normal and pan-cancer tissues along with prominent putative prognostic biomarker potentials. The genes and were found to be upregulated in the proneural subtype, while in the mesenchymal subtype of glioblastoma exhibits good prognostic potential. The mutational analysis also revealed the benign, possibly, and probably damaging substitution mutations. The correlation between the DEG and survival in glioblastoma was evaluated using the Kaplan-Meier plots, and had a greater life expectancy of 60.25 months. Overall, this study identified key candidate genes that might serve as predictive biomarkers for glioblastoma.
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http://dx.doi.org/10.3389/fgene.2022.832742 | DOI Listing |
Eur J Pharmacol
December 2024
The School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, 510006, PR China. Electronic address:
Glioblastoma multiforme (GBM) is a highly heterogeneous and aggressive brain tumor, which presents significant challenges for treatment in clinical settings. Phosphodiesterase 4 (PDE4) inhibitors can prevent the degradation of cAMP and have been used as a potential targeted therapeutic approach for different cancer types. However, its clinical use is restricted by the side effects such as nausea and vomiting.
View Article and Find Full Text PDFJ Biol Chem
December 2024
Department of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14853, USA; Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, 14853, USA. Electronic address:
Phosphatase and Tensin Homologue (PTEN) is one of the most frequently lost tumor suppressors in cancer and the predominant negative regulator of the PI3K/AKT signaling axis. A growing body of evidence has highlighted the loss of PTEN with immuno-modulatory functions including the upregulation of the programmed death ligand-1 (PD-L1), an altered tumor derived secretome that drives an immunosuppressive tumor immune microenvironment (TIME), and resistance to certain immunotherapies. Given their roles in immunosuppression and tumor growth, we examined whether the loss of PTEN would impact the biogenesis, cargo, and function of extracellular vesicles (EVs) in the context of the anti-tumor associated cytokine interferon-γ (IFN-γ).
View Article and Find Full Text PDFBiomaterials
December 2024
Department of Neurosurgery, Yale University, New Haven, CT, 06511, USA; Department of Biomedical Engineering, Yale University, New Haven, CT, 06510, USA. Electronic address:
Glioblastoma (GBM), the most common primary brain tumor, lacks effective treatments. Emerging evidence suggests mitochondria as a promising therapeutic target, albeit successfully targeting represents a major challenge. Recently, we discovered a group of triterpenes that can self-assemble into nanoparticles (NPs) for cancer treatment.
View Article and Find Full Text PDFBiomater Adv
December 2024
Department of Chemistry and the Natural Science Research Institute, Myongji University, 116 Myongji-ro, Yongin-si 17058, Republic of Korea. Electronic address:
MicroRNAs (miRNAs) are non-coding, endogenous small single-stranded RNA molecules involved in post-transcriptional regulation of gene expression. It has been demonstrated that dysregulation of miRNA plays a major role in tumor formation, proliferation, and metastasis. Therefore, the delivery of anti-miRNA oligonucleotides to block the activity of these oncogenic miRNAs is a high-potential anti-cancer therapy approach.
View Article and Find Full Text PDFNeuro Oncol
December 2024
Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Background: Selinexor is a selective inhibitor of exportin-1 (XPO1), a key mediator of the nucleocytoplasmic transport for molecules critical to tumor cell survival. Selinexor's lethality is generally associated with the induction of apoptosis, and in some cases, with autophagy-induced apoptosis. We performed this study to determine Selinexor's action in glioblastoma (GBM) cells, which are notoriously resistant to apoptosis.
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