Cao Xu, Zheng Shi-Hao, Shen Jiu-Mei, Li Si-Ze, Hou Li, Zhang Jia-Xin, Li Xiao-Ke, Du Hong-Bo, Zhang Li-Ping, Ye Yong-An, Zao Xiao-Bin
Department of Spleen and Gastroenterology, Dongzhimen Hospital of Beijing University of Chinese Medicine, Beijing 100700, China.
Department of Gastroenterology, The First Affiliated Hospital of Dalian Medical University, Dalian 116000, Liaoning Province, China.
World J Gastrointest Oncol. 2025 Jul 15;17(7):105981. doi: 10.4251/wjgo.v17.i7.105981.
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.
To offer a more systematic and comprehensive elucidation of the involvement of UGDH in the onset and progression of various malignancies.
The role of UGDH in cancer was investigated public databases. The data were analyzed various R packages and websites, including TISIDB, cBioPortal, STRING, Cytoscape, GSCALite, and CancerSEA. A rat hepatocellular carcinoma (HCC) model was established 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.
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.
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.
UDP-葡萄糖6-脱氢酶（UGDH）是葡萄糖醛酸代谢中的关键酶，在多种癌症发展信号通路中起关键介导作用。
更系统、全面地阐明UGDH在各种恶性肿瘤发生和发展中的作用。
通过公共数据库研究UGDH在癌症中的作用。使用包括TISIDB、cBioPortal、STRING、Cytoscape、GSCALite和CancerSEA在内的各种R包和网站对数据进行分析。通过腹腔注射二乙基亚硝胺建立大鼠肝细胞癌（HCC）模型。对肝组织进行苏木精-伊红染色、Masson染色、Ki67和UGDH免疫组织化学染色以及ARG1免疫荧光染色。采用实时定量PCR和蛋白质印迹法检测UGDH表达。在Huh7细胞中敲低UGDH基因，并进行CCK8和裸鼠肿瘤异种移植实验。
UGDH高表达与HCC、肺腺癌、肺鳞状细胞癌和肉瘤患者的不良临床结局相关，并且在分子和免疫亚型中差异表达。UGDH主要参与戊糖和葡萄糖醛酸相互转化途径。在大多数癌症中，其表达与辅助性T细胞、中央记忆性T细胞和Th2细胞呈正相关。此外，实验结果表明HCC组织中UGDH表达升高，其下调抑制HCC细胞增殖。
我们的研究表明，UGDH可能是许多癌症，尤其是肝癌和肺癌中有价值的预后生物标志物和潜在治疗靶点。UGDH可能通过调节戊糖和葡萄糖醛酸相互转化途径促进HCC细胞增殖。
