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Volume 10,Issue 4

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6 February 2026
Glucose-6-Phosphate Dehydrogenase is a Prognostic Biomarker and Correlated with Immune Infiltrates in Hepatocellular Carcinoma
Yiming Niu ,  Qi Zhu ,  Jintang Jia
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1 Gansu Provincial Maternity and Child-care Hospital /Gansu Provincial Central Hospital, Lanzhou 730000, Gansu, China,
2 Gansu Provincial Maternity and Child-care Hospital / Gansu Provincial Central Hospital, Lanzhou 730000, Gansu, China,
PAR 2026 , 10(1), 8–21; https://doi.org/10.26689/par.v10i1.13200
© 2026 by the Authors. Licensee Whioce Publishing, Singapore. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Objective: To investigate the correlation between the expression of glucose-6-phosphate dehydrogenase (G6PD) and the clinicopathological characteristics, prognosis and immune cell infiltration of hepatocellular carcinoma (HCC). Methods: The expression of G6PD in liver cancer tissues and normal tissues is extracted from TCGA and GEO databases, validated by immunohistochemistry, and the correlation between G6PD expression and clinical features is analyzed. The clinical significance of G6PD in liver cancer is assessed by Kaplan-Meier, Cox regression, and prognostic line graph models. Functional enrichment analysis is performed by protein-protein interaction (PPI) network, GO/KEGG, GSEA and for G6PD-associated differentially expressed genes (DEGs). TIMER and ssGSEA packages are used to assess the correlation between expression and the level of immune cell infiltration. Results: Analysis of TCGA and GEO datasets revealed that G6PD expression is significantly upregulated in hepatocellular carcinoma tissues (P < 0.001). G6PD expression is associated with histological grade, pathological stage, T-stage, vascular infiltration, and AFP level (P < 0.05); HCC patients in the low G6PD expression group had longer overall survival and better prognosis compared with the high G6PD expression group (P < 0.05). The level of G6PD expression affects the levels of macrophages, dendritic cells, B cells, and follicular helper T cells in the tumor microenvironment. Conclusion: High expression of G6PD is a potential biomarker for poor prognosis of hepatocellular carcinoma, and G6PD may be a target for immunotherapy of HCC.

References
Sung H, Ferlay J, Siegel R, et al., 2021, Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 71(3): 209–249.
Llovet J, Kelley R, Villanueva A, et al., 2021, Hepatocellular Carcinoma. Nature Reviews Disease Primers, 7(1): 6.
Chu P, Chan S, 2021, Cure the Incurable? Recent Breakthroughs in Immune Checkpoint Blockade for Hepatocellular Carcinoma. Cancers, 13(21): 5295.
Marrero J, Kulik L, Sirlin C, et al., 2018, Diagnosis, Staging, and Management of Hepatocellular Carcinoma: 2018 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology, 68(2): 723–750.
Boroughs L, DeBerardinis R, 2015, Metabolic Pathways Promoting Cancer Cell Survival and Growth. Nature Cell Biology, 17(4): 351–359.
Wood T, 1986, Physiological Functions of the Pentose Phosphate Pathway. Cell Biochemistry and Function, 4(4): 241–247.
Wang A, Chen B, Jian S, et al., 2021, miR-206-G6PD Axis Regulates Lipogenesis and Cell Growth in Hepatocellular Carcinoma Cell. Anti-Cancer Drugs, 32(5): 508–516.
Yan Y, Wang J, Dong X, et al., 2022, Quantitative Proteomic Analysis of Hepatic Tissue in Allotetraploid Hybridized from Red Crucian Carp and Common Carp Identified Crucial Proteins and Pathways Associated with Metabolism and Growth Rate. Proteomics, 22(4): e2100115.
Yang H, Wu Y, Yen W, et al., 2019, The Redox Role of G6PD in Cell Growth, Cell Death, and Cancer. Cells, 8(9): 1055.
Wang J, Yuan W, Chen Z, et al., 2012, Overexpression of G6PD Is Associated with Poor Clinical Outcome in Gastric Cancer. Tumour Biology, 33(1): 95–101.
Dong T, Kang X, Liu Z, et al., 2016, Altered Glycometabolism Affects Both Clinical Features and Prognosis of Triple-Negative and Neoadjuvant Chemotherapy-Treated Breast Cancer. Tumour Biology, 37(6): 8159–8168.
Ohl F, Jung M, Radonić A, et al., 2006, Identification and Validation of Suitable Endogenous Reference Genes for Gene Expression Studies of Human Bladder Cancer. The Journal of Urology, 175(5): 1915–1920.
Van Driel B, Valet G, Lyon H, et al., 1999, Prognostic Estimation of Survival of Colorectal Cancer Patients with the Quantitative Histochemical Assay of G6PDH Activity and the Multiparameter Classification Program CLASSIF1. Cytometry, 38(4): 176–183.
Fang Z, Jiang C, Feng Y, et al., 2016, Effects of G6PD Activity Inhibition on the Viability, ROS Generation and Mechanical Properties of Cervical Cancer Cells. Biochimica et Biophysica Acta, 1863(9): 2245–2254.
Budihardjo I, Walker D, Svingen P, et al., 1998, 6-Aminonicotinamide Sensitizes Human Tumor Cell Lines to Cisplatin. Clinical Cancer Research, 4(1): 117–130.
Polimeni M, Voena C, Kopecka J, et al., 2011, Modulation of Doxorubicin Resistance by the Glucose-6-Phosphate Dehydrogenase Activity. The Biochemical Journal, 439(1): 141–149.
Mele L, Paino F, Papaccio F, et al., 2018, A New Inhibitor of Glucose-6-Phosphate Dehydrogenase Blocks Pentose Phosphate Pathway and Suppresses Malignant Proliferation and Metastasis in Vivo. Cell Death & Disease, 9(5): 572.
Zhang H, Zhang Z, Du G, et al., 2019, Nrf2 Promotes Breast Cancer Cell Migration via Up-Regulation of G6PD/HIF-1α/Notch1 Axis. Journal of Cellular and Molecular Medicine, 23(5): 3451–3463.
Chen J, Cao S, Situ B, et al., 2018, Metabolic Reprogramming-Based Characterization of Circulating Tumor Cells in Prostate Cancer. Journal of Experimental & Clinical Cancer Research, 37(1): 127.
Hu T, Zhang C, Tang Q, et al., 2013, Variant G6PD Levels Promote Tumor Cell Proliferation or Apoptosis via the STAT3/5 Pathway in the Human Melanoma Xenograft Mouse Model. BMC Cancer, 13: 251.
Hong X, Song R, Song H, et al., 2014, PTEN Antagonises Tcl1/hnRNPK-Mediated G6PD pre-mRNA Splicing Which Contributes to Hepatocarcinogenesis. Gut, 63(10): 1635–1647.
Yin X, Tang B, Li J, et al., 2017, ID1 Promotes Hepatocellular Carcinoma Proliferation and Confers Chemoresistance to Oxaliplatin by Activating Pentose Phosphate Pathway. Journal of Experimental & Clinical Cancer Research, 36(1): 166.
Cao H, Chen X, Wang Z, et al., 2020, The Role of MDM2-p53 Axis Dysfunction in the Hepatocellular Carcinoma Transformation. Cell Death Discovery, 6: 53.
Levine A, 2018, Reviewing the Future of the P53 Field. Cell Death and Differentiation, 25(1): 1–2.
Chang H, Li J, Luo Y, et al., 2021, TFB2M Activates Aerobic Glycolysis in Hepatocellular Carcinoma Cells through the NAD⁺/SIRT3/HIF-1α Signaling. Journal of Gastroenterology and Hepatology, 36(10): 2978–2988.
Geng X, Geng Z, Li H, et al., 2020, Over-Expression of TFB2M Facilitates Cell Growth and Metastasis via Activating ROS–Akt–NF-κB Signalling in Hepatocellular Carcinoma. Liver International, 40(7): 1756–1769.
Xu L, Yang C, Ma J, et al., 2021, NAMPT-Mediated NAD⁺ Biosynthesis Suppresses Activation of Hepatic Stellate Cells and Protects against CCl₄-Induced Liver Fibrosis in Mice. Human & Experimental Toxicology, 40(12 Suppl): S666–S675.
Schuster S, Penke M, Gorski T, et al., 2015, FK866-Induced NAMPT Inhibition Activates AMPK and Downregulates mTOR Signaling in Hepatocarcinoma Cells. Biochemical and Biophysical Research Communications, 458(2): 334–340.
Lennicke C, Cochemé H, 2021, Redox Metabolism: ROS as Specific Molecular Regulators of Cell Signaling and Function. Molecular Cell, 81(18): 3691–3707.
Simon-Molas H, Vallvé-Martínez X, Caldera-Quevedo I, et al., 2021, TP53-Induced Glycolysis and Apoptosis Regulator (TIGAR) Is Upregulated in Lymphocytes Stimulated with Concanavalin A. International Journal of Molecular Sciences, 22(14): 7436.
Kowalik M, Guzzo G, Morandi A, et al., 2016, Metabolic Reprogramming Identifies the Most Aggressive Lesions at Early Phases of Hepatic Carcinogenesis. Oncotarget, 7(22): 32375–32393.
Udono H, Nishida M, 2022, Pharmacological Effects on Anaplerotic Pathways Alter the Metabolic Landscape in the Tumor Microenvironment, Causing Unpredictable, Sustained Anti-Tumor Immunity. International Immunology, 34(3): 133–140.
Durgeau A, Virk Y, Corgnac S, et al., 2018, Recent Advances in Targeting CD8 T-Cell Immunity for More Effective Cancer Immunotherapy. Frontiers in Immunology, 9: 14.
Lim A, Rathmell W, Rathmell J, 2020, The Tumor Microenvironment as a Metabolic Barrier to Effector T Cells and Immunotherapy. eLife, 9: e55185.
Odegaard J, Chawla A, 2013, The Immune System as a Sensor of the Metabolic State. Immunity, 38(4): 644–654.
Gu M, Zhou X, Sohn J, et al., 2021, NF-κB-Inducing Kinase Maintains T Cell Metabolic Fitness in Antitumor Immunity. Nature Immunology, 22(2): 193–204.
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