Abstract
Metabolic pattern reconstruction is an important factor in tumor progression. Metabolism of tumor cells is characterized by abnormal increase in anaerobic glycolysis, regardless of high oxygen concentration, resulting in a significant accumulation of energy from glucose sources. These changes promotes rapid cell proliferation and tumor growth, which is further referenced a process known as the Warburg effect. The current study reconstructed the metabolic pattern in progression of cancer to identify genetic changes specific in cancer cells. A total of 12 common types of solid tumors were included in the current study. Gene set enrichment analysis (GSEA) was performed to analyze 9 glycolysis-related gene sets, which are implicated in the glycolysis process. Univariate and multivariate analyses were used to identify independent prognostic variables for construction of a nomogram based on clinicopathological characteristics and a glycolysis-related gene prognostic index (GRGPI). The prognostic model based on glycolysis genes showed high area under the curve (AUC) in LIHC (Liver hepatocellular carcinoma). The findings of the current study showed that 8 genes (AURKA, CDK1, CENPA, DEPDC1, HMMR, KIF20A, PFKFB4, STMN1) were correlated with overall survival (OS) and recurrence-free survival (RFS). Further analysis showed that the prediction model accurately distinguished between high- and low-risk cancer patients among patients in different clusters in LIHC. A nomogram with a well-fitted calibration curve based on gene expression profiles and clinical characteristics showed good discrimination based on internal and external cohorts. These findings indicate that changes in expression level of metabolic genes implicated in glycolysis can contribute to reconstruction of tumor-related microenvironment.
Highlights
Metabolic pattern reconstruction is an important factor in tumor progression
A total of 12 solid tumors with complete clinical information and gene expression profiles including BLCA, BRCA, COAD, HNSC, KIRC, KIRP, LIHC, LUAD, LUSC, OV, PRAD, and THCA were included in the present study
The current study developed and optimized a novel 8-gene signature for identifying outcomes and recurrence in Hepatocellular carcinoma (HCC) patients
Summary
Metabolism of tumor cells is characterized by abnormal increase in anaerobic glycolysis, regardless of high oxygen concentration, resulting in a significant accumulation of energy from glucose sources These changes promotes rapid cell proliferation and tumor growth, which is further referenced a process known as the Warburg effect. A nomogram with a well-fitted calibration curve based on gene expression profiles and clinical characteristics showed good discrimination based on internal and external cohorts These findings indicate that changes in expression level of metabolic genes implicated in glycolysis can contribute to reconstruction of tumor-related microenvironment. Warburg effect represents change in glucose utilization by tumor cells from oxidative phosphorylation to glycolysis, which is acknowledged as a major feature hallmark of tumors[6,7] This change in energy metabolism is determined by complex factors, including pressure on tumor microenvironment and genetic changes[8,9,10,11]. Cox multivariate hazard ratio analysis showed that the risk score performed better compared with other clinical variable in evaluating patient prognosis
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