Glycolysis-related gene expression profiling serves as a novel prognosis risk predictor for human hepatocellular carcinoma

被引:24
|
作者
Zhang, Lingyu [1 ]
Li, Yu [2 ]
Dai, Yibei [1 ]
Wang, Danhua [1 ]
Wang, Xuchu [1 ]
Cao, Ying [1 ]
Liu, Weiwei [1 ]
Tao, Zhihua [1 ]
机构
[1] Zhejiang Univ, Dept Lab Med, Affiliated Hosp 2, Sch Med, 88 Jiefang Rd, Hangzhou 310009, Peoples R China
[2] Bengbu Med Coll, Dept Biochem & Mol Biol, Bengbu 233030, Anhui, Peoples R China
基金
中国国家自然科学基金;
关键词
B-CELLS; AURORA KINASE; LIVER-CANCER; METABOLISM; SURVIVAL; RESISTANCE; INHIBITORS; CROSSTALK; BIOMARKER; STEMNESS;
D O I
10.1038/s41598-021-98381-2
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
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页数:21
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