Abstract
BackgroundMetabolic abnormalities have recently been widely studied in various cancer types. This study aims to explore the expression profiles of metabolism-related genes (MRGs) in endometrial cancer (EC).MethodsWe analyzed the expression of MRGs using The Cancer Genome Atlas (TCGA) data to screen differentially expressed MRGs (DE-MRGs) significantly correlated with EC patient prognosis. Functional pathway enrichment analysis of the DE-MRGs was performed. LASSO and Cox regression analyses were performed to select MRGs closely related to EC patient outcomes. A prognostic signature was developed, and the efficacy was validated in part of and the entire TCGA EC cohort. Moreover, we developed a comprehensive nomogram including the risk model and clinical features to predict EC patients’ survival probability.ResultsForty-seven DE-MRGs were significantly correlated with EC patient prognosis. Functional enrichment analysis showed that these MRGs were highly enriched in amino acid, glycolysis, and glycerophospholipid metabolism. Nine MRGs were found to be closely related to EC patient outcomes: CYP4F3, CEL, GPAT3, LYPLA2, HNMT, PHGDH, CKM, UCK2 and ACACB. Based on these nine DE-MRGs, we developed a prognostic signature, and its efficacy in part of and the entire TCGA EC cohort was validated. The nine-MRG signature was independent of other clinical features, and could effectively distinguish high- and low-risk EC patients and predict patient OS. The nomogram showed excellent consistency between the predictions and actual survival observations.ConclusionsThe MRG prognostic model and the comprehensive nomogram could guide precise outcome prediction and rational therapy selection in clinical practice.
Highlights
Metabolic abnormalities have recently been widely studied in various cancer types
The metabolic phenotype of cancer cells is heterogeneous in various cancer types; for example, while several malignant tumors mainly rely on glycolysis, others present a metabolic phenotype mediated by oxidative phosphorylation [5, 6]
We focused on the metabolism-related gene expression alterations of The Cancer Genome Atlas (TCGA) endometrial cancer (EC) patients and obtained prognostic dysregulated metabolism-related genes (MRGs)
Summary
Metabolic abnormalities have recently been widely studied in various cancer types. This study aims to explore the expression profiles of metabolism-related genes (MRGs) in endometrial cancer (EC). The metabolic phenotype of cancer cells is heterogeneous in various cancer types; for example, while several malignant tumors mainly rely on glycolysis, others present a metabolic phenotype mediated by oxidative phosphorylation [5, 6]. Through reprogramming tumor microenvironments, catabolic and anabolic metabolism is essential for cancer cells to sustain energy supply and biomass synthesis [7,8,9]. While the underlying processes and molecular alterations of metabolic programming in various cancers have been well elucidated, the expression patterns of metabolism-related genes in endometrial cancer are still unclear
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