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©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
Pan-cancer analysis of UDP-glucose 6-dehydrogenase in human tumors and its function in hepatocellular carcinoma
Xu Cao, Shi-Hao Zheng, Jiu-Mei Shen, Si-Ze Li, Li Hou, Jia-Xin Zhang, Xiao-Ke Li, Hong-Bo Du, Li-Ping Zhang, Yong-An Ye, Xiao-Bin Zao
Xu Cao, Shi-Hao Zheng, Si-Ze Li, Jia-Xin Zhang, Xiao-Ke Li, Hong-Bo Du, Li-Ping Zhang, Yong-An Ye, Department of Spleen and Gastroenterology, Dongzhimen Hospital of Beijing University of Chinese Medicine, Beijing 100700, China
Xu Cao, Department of Gastroenterology, The First Affiliated Hospital of Dalian Medical University, Dalian 116000, Liaoning Province, China
Jiu-Mei Shen, Department of Pathology, Xiamen Hospital of Chinese Medicine, Xiamen 361000, Fujian Province, China
Li Hou, Department of Oncology and Hematology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100029, China
Jia-Xin Zhang, Xiao-Ke Li, Hong-Bo Du, Yong-An Ye, Institute of Liver Diseases, Beijing University of Chinese Medicine, Beijing 100700, China
Xiao-Bin Zao, Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China
Xiao-Bin Zao, Ministry of Science, Xiamen Hospital of Chinese Medicine, Xiamen 361000, Fujian Province, China
Co-first authors: Xu Cao and Shi-Hao Zheng.
Co-corresponding authors: Yong-An Ye and Xiao-Bin Zao.
Author contributions: Cao X and Zheng SH made equal contributions to performing experiments, data analysis, and writing of the manuscript; Shen JM contributed to clinical sample collection, experiments, and data analysis; Li SZ, Hou L, Zhang JX, and Li XK collected and analyzed data; Du HB and Zhang LP validated the data analysis; Cao X and Zheng SH contributed equally to this work as co-first authors. Zao XB and Ye YA designed the research, performed data analysis, contributed to the conceptualization of the paper, revised the manuscript, and worked together to ensure the smooth progress of the study; therefore, they are designated as co-corresponding authors.
Supported by National Natural Science Foundation of China, No. 82405314; Horizontal Project of Dongzhimen Hospital, No. HX-DZM-202405; Project of Beijing University of Chinese Medicine, No. DZMG-QNZX-24015; and Traditional Chinese Medicine Foundation of Xiamen, No. XWZY-2023-0616.
Institutional review board statement: The Ethics Committee of Xiamen Hospital of Traditional Chinese Medicine approved the investigation of clinical samples (2020-K030-01).
Institutional animal care and use committee statement: The Ethics Committee of Laboratory Animals of Dongzhimen Hospital of Beijing University of Chinese Medicine approved the animal study (No. 21-10-01 and 21-46-01).
Conflict-of-interest statement: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: Not applicable.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Xiao-Bin Zao, PhD, Assistant Professor, Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, No. 116 Cuiping West Road, Tongzhou District, Beijing 100700, China.
a3417@bucm.edu.cn
Received: February 14, 2025
Revised: March 26, 2025
Accepted: May 21, 2025
Published online: July 15, 2025
Processing time: 152 Days and 10.5 Hours
BACKGROUND
UDP-glucose 6-dehydrogenase (UGDH) is a key enzyme in glucuronic acid metabolism and acts as a key mediator in several cancer developmental signaling pathways.
AIM
To offer a more systematic and comprehensive elucidation of the involvement of UGDH in the onset and progression of various malignancies.
METHODS
The role of UGDH in cancer was investigated via public databases. The data were analyzed via various R packages and websites, including TISIDB, cBioPortal, STRING, Cytoscape, GSCALite, and CancerSEA. A rat hepatocellular carcinoma (HCC) model was established via the intraperitoneal injection of diethylnitrosamine. Hematoxylin-eosin staining, Masson staining, Ki67 and UGDH immunohistochemical staining, and ARG1 immunofluorescence staining of liver tissues were performed. Real-time quantitative PCR and Western blotting were used to detect UGDH expression. The UGDH gene was knocked down in Huh7 cells, and CCK8 and nude mouse tumor xenograft assays were performed.
RESULTS
High UGDH expression is associated with poor clinical outcomes in HCC, lung adenocarcinoma, lung squamous cell carcinoma, and sarcoma patients and is differentially expressed across molecular and immune subtypes. UGDH is primarily involved in the pentose and glucuronate interconversion pathway. Its expression is positively correlated with T helper, Tcm, and Th2 cells in most cancers. Moreover, experimental results demonstrated that UGDH expression is elevated in HCC tissues and that its downregulation inhibits HCC cell proliferation.
CONCLUSION
Our study revealed that UGDH could be a valuable prognostic biomarker and potential therapeutic target in many cancers, especially liver and lung cancer. UGDH could promote HCC cell proliferation, potentially by modulating the pentose and glucuronate interconversion pathways.
Core Tip: Our study identified UDP-glucose 6-dehydrogenase (UGDH) as a potential prognostic biomarker and therapeutic target for many cancers, especially liver and lung cancer. UGDH promotes hepatocellular carcinoma cell proliferation, possibly by modulating the pentose and glucuronate interconversion pathway.
