Differential gene expression analysis supports dysregulation of mitochondrial activity as a new perspective for glioblastoma's aggressiveness

Abstract

Brain cancer is considered one of the most aggressive and lethal types of cancer, including primary tumors, being subdivided into milder forms such as low-grade gliomas and glioblastoma, considered the most aggressive form with higher invasion. Among the hallmarks of glioblastoma, the deregulation of mitochondrial metabolism has not yet been fully elucidated. Therefore, the search for mitochondrial biomarkers that can be used as indicators of the progression of this type of cancer is necessary. The aim of this study was to investigate the difference in gene expression between astrocytoma-type gliomas and glioblastomas, and how genes involved in mitochondrial metabolism can influence the proliferative cascade and be associated with tumor invasion. From the differential analysis of glioblastoma expression when compared to the milder form, 11 differentially expressed genes (DEGs) were found in our study, six of which were upregulated (ATP5MGL, C15orf48, MCUB, TERT, AGXT and CYP27B1) and four downregulated (SLC2A4, GK2, SLC25A48, ETNPPL and HMGCS2). To validate the findings, we used other independent bulk RNA-seq datasets and evaluated the number of normalized counts of the DEGs founded. Among these genes, we highlight that none of them had been reported in glioblastoma until this research, and we suggest these genes as possible biomarkers to be further explored, since they are associated with essential pathways for the tumor, such as glucose metabolization, gluconeogenesis, calcium and vitamin D metabolism, tumor progression and activation of the invasion cascade.

Keywords

• Astrocytoma
• Glioblastoma
• Gene expression
• Glycolysis
• Oxidative phosphorylation