Effects of Glycolysis-Related Genes on Prognosis and the Tumor Microenvironment of Hepatocellular Carcinoma

Background: Hepatocellular carcinoma (HCC) is a common and deadly malignancy worldwide. Current treatment methods for hepatocellular carcinoma have many disadvantages; thus, it is urgent to improve the efficacy of these therapies. Glycolysis is critical in the occurrence and development of tumors. H...

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Main Authors: Ju-Yan Zheng (Author), Jun-Yan Liu (Author), Tao Zhu (Author), Chong Liu (Author), Ying Gao (Author), Wen-Ting Dai (Author), Wei Zhuo (Author), Xiao-Yuan Mao (Author), Bai-Mei He (Author), Zhao-Qian Liu (Author)
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Published: Frontiers Media S.A., 2022-07-01T00:00:00Z.
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042 |a dc 
100 1 0 |a Ju-Yan Zheng  |e author 
700 1 0 |a Ju-Yan Zheng  |e author 
700 1 0 |a Jun-Yan Liu  |e author 
700 1 0 |a Jun-Yan Liu  |e author 
700 1 0 |a Tao Zhu  |e author 
700 1 0 |a Tao Zhu  |e author 
700 1 0 |a Chong Liu  |e author 
700 1 0 |a Chong Liu  |e author 
700 1 0 |a Ying Gao  |e author 
700 1 0 |a Ying Gao  |e author 
700 1 0 |a Wen-Ting Dai  |e author 
700 1 0 |a Wen-Ting Dai  |e author 
700 1 0 |a Wei Zhuo  |e author 
700 1 0 |a Wei Zhuo  |e author 
700 1 0 |a Xiao-Yuan Mao  |e author 
700 1 0 |a Xiao-Yuan Mao  |e author 
700 1 0 |a Bai-Mei He  |e author 
700 1 0 |a Zhao-Qian Liu  |e author 
700 1 0 |a Zhao-Qian Liu  |e author 
245 0 0 |a Effects of Glycolysis-Related Genes on Prognosis and the Tumor Microenvironment of Hepatocellular Carcinoma 
260 |b Frontiers Media S.A.,   |c 2022-07-01T00:00:00Z. 
500 |a 1663-9812 
500 |a 10.3389/fphar.2022.895608 
520 |a Background: Hepatocellular carcinoma (HCC) is a common and deadly malignancy worldwide. Current treatment methods for hepatocellular carcinoma have many disadvantages; thus, it is urgent to improve the efficacy of these therapies. Glycolysis is critical in the occurrence and development of tumors. However, survival and prognosis biomarkers related to glycolysis in HCC patients remain to be fully identified.Methods: Glycolysis-related genes (GRGs) were downloaded from "The Molecular Signatures Database" (MSigDB), and the mRNA expression profiles and clinical information of HCC patients were obtained from TCGA. Consensus clustering was performed to classify the HCC patients into two subgroups. We used the least absolute shrinkage and selection operator (LASSO) regression analysis to construct the risk signature model. Kaplan-Meier (K-M) survival analysis was performed to evaluate the prognostic significance of the risk model, and the receiver operating characteristic (ROC) curve analysis was used to evaluate the prediction accuracy. The independent prediction ability of the risk model was validated by univariate and multivariate Cox regression analyses. The differences of immune infiltrates and relevant oncogenic signaling between different risk groups were compared. Finally, biological experiments were performed to explore the functions of screened genes.Results: HCC patients were classified into two subgroups, according to the expression of prognostic-related GRGs. Almost all GRGs categorized in cluster 2 showed upregulated expressions, whereas GRGs in cluster 1 conferred survival advantages. GSEA identified a positive correlation between cluster 2 and the glycolysis process. Ten genes were selected for risk signature construction. Patients were assigned to high-risk and low-risk groups based on the median risk score, and K-M survival analysis indicated that the high-risk group had a shorter survival time. Additionally, the risk gene signature can partially affect immune infiltrates within the HCC microenvironment, and many oncogenic pathways were enriched in the high-risk group, including glycolysis, hypoxia, and DNA repair. Finally, in vitro knockdown of ME1 suppressed proliferation, migration, and invasion of hepatocellular carcinoma cells.Conclusion: In our study, we successfully constructed and verified a novel glycolysis-related risk signature for HCC prognosis prediction, which is meaningful for classifying HCC patients and offers potential targets for the treatment of hepatocellular carcinoma. 
546 |a EN 
690 |a hepatocellular carcinoma 
690 |a glycolysis 
690 |a prognosis 
690 |a risk signature 
690 |a immune infiltrates 
690 |a Therapeutics. Pharmacology 
690 |a RM1-950 
655 7 |a article  |2 local 
786 0 |n Frontiers in Pharmacology, Vol 13 (2022) 
787 0 |n https://www.frontiersin.org/articles/10.3389/fphar.2022.895608/full 
787 0 |n https://doaj.org/toc/1663-9812 
856 4 1 |u https://doaj.org/article/74c100d8aa6b42b0bb0d768b4f9d12c4  |z Connect to this object online.