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ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1529029
This article is part of the Research Topic Frontier Developments in Immunotherapy for Hepatocellular Carcinoma View all 3 articles
The Role of Transketolase in the Immunotherapy and Prognosis of Hepatocellular Carcinoma: A Multi-Omics Approach
Provisionally accepted- Affiliated Hospital of Zunyi Medical University, Zunyi, China
Objective: To explore the role of transketolase (TKT) in the immunotherapy and prognosis of hepatocellular carcinoma (HCC).TKT expression across various cancers and its associations with tumor immunity and prognosis were analyzed using nomogram models. A multi-omics approach was employed, including bulk RNA-seq analysis, methylation profiling, single-cell analysis, and spatial transcriptomics. Experimental methods included RT-qPCR, siRNA transfection, luciferase reporter assay, and chromatin immunoprecipitation.Results: TKT was significantly upregulated in multiple cancers and correlated with immune cell infiltration, particularly in HCC. Elevated TKT expression was associated with poor overall survival (OS) in HCC and was an independent prognostic factor (p < 0.05). Drug sensitivity analysis suggested that Higher TKT expression was associated with reduced sensitivity to several chemotherapeutic agents, including sorafenib (p < 0.01). Furthermore, hypermethylation of the TKT promoter and low TKT expression were linked to improved OS in HCC (log-rank test p = 0.005). Single-cell analysis revealed that TKT was predominantly expressed in the monocyte/macrophage cluster associated with HCC, and pseudo-time series analysis highlighted TKT's role in cell differentiation within this cluster. Spatial transcriptomics confirmed the close association between TKT and macrophage distribution in HCC. Moreover, STAT3 was found to directly regulate TKT expression by binding to its promoter region.Our findings suggest that TKT may play a role in tumor immunity and prognosis in HCC. Although these results provide insights into the potential involvement of TKT in immune cell infiltration and survival outcomes, further studies are required to fully elucidate its role in immunotherapy.
Keywords: Transketolase, TKT, Hepatocellular Carcinoma, Hep-G2, Pentose Phosphate Pathway
Received: 15 Nov 2024; Accepted: 12 Mar 2025.
Copyright: © 2025 Gu, Zhou, Yao, Yang, Gu, Mu and Zhao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Lijin Zhao, Affiliated Hospital of Zunyi Medical University, Zunyi, China
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