Abstract
Now, numerous exciting findings have been yielded in the field of energy metabolism within glioma cells. In addition to aerobic glycolysis, multiple catabolic pathways are employed for energy production. However, the prognostic significance of energy metabolism in glioma remains obscure. Here, we explored the relationship between energy metabolism gene profile and outcome of diffuse glioma patients using The Cancer Genome Altas (TCGA) and Chinese Glioma Genome Altas (CGGA) datasets. Based on the gene expression profile, consensus clustering identified two robust clusters of glioma patients with distinguished prognostic and molecular features. With the Cox proportional hazards model with elastic net penalty, an energy metabolism-related signature was built to evaluate patients’ prognosis. Kaplan-Meier analysis found that the acquired signature could differentiate the outcome of low and high-risk groups of patients in both cohorts. Moreover, the signature, significantly associated with the clinical and molecular features, could serve as an independent prognostic factor for glioma patients. Gene Ontology (GO) and Gene Set Enrichment Analysis (GSEA) showed that gene sets correlated with high-risk group were involved in immune and inflammatory response, with the low-risk group were mainly related to glutamate receptor signaling pathway. Our results provided new insight into energy metabolism role in diffuse glioma.
Highlights
Energy metabolic reprogramming has been a hallmark of cancer cells, which enable tumor cells to generate ATP for maintaining the reduction-oxidation balance and macromolecular biosynthesis—processes that are required for cell growth, proliferation and migration [1]
To profile the energy metabolism status of glioma, a cohort of 550 patients with RNA sequencing data and clinical information was obtained from the The Cancer Genome Altas (TCGA) database
Significance analysis of microarray (SAM) and Gene Ontology (GO) analyses found 25 carbohydrate metabolism genes were differentially expressed between isocitrate dehydrogenase (IDH)-wt and IDH-mut lower grade glioma (LGG) (Supplementary Figure 1D)
Summary
Energy metabolic reprogramming has been a hallmark of cancer cells, which enable tumor cells to generate ATP for maintaining the reduction-oxidation balance and macromolecular biosynthesis—processes that are required for cell growth, proliferation and migration [1]. In comparison to normal cells, tumor cells prefer to incomplete, non-oxidative metabolism of glucose. Some tumor cells are predominantly glycolytic, whereas others with the given tumor have an oxidative phosphorylation (OXPHOS) metabolic phenotype [3, 4]. Increasing evidences show that there is a metabolic symbiosis between glycolytic and oxidative tumor cells. Lactate and pyruvate generated by glycolysis can be transferred to and used as substrates for tricarboxylic acid (TCA) intermediates and ATP production by the neighbor cancer cells [5]. Malignant tumor cells can take up free fatty acids and ketones released by adjacent catabolic cells, which will fuel the mitochondrial OXPHOS for energy production [6, 7]. It has been reported that glutamine can be metabolized by TCA cycle to produce energy [8]
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