Department of Hepatobiliary and Pancreatic Surgery, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang 321000, China.
Department of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital, Zhejiang Shuren University, Shulan International Medical College, Hangzhou, Zhejiang, China.
Clin Res Hepatol Gastroenterol. 2023 Dec;47(10):102248. doi: 10.1016/j.clinre.2023.102248. Epub 2023 Nov 16.
Glutamine synthetase (GS) is an enzyme that converts ammonia and glutamate to glutamine using adenosine triphosphate. GS is expressed in the brain, kidney, and liver tissues under normal physiological conditions. GS is involved in abnormal lipid metabolism of the liver by catalyzing de novo synthesis of glutamine, thereby inducing liver inflammation. Metabolic dysfunction-associated steatotic liver diseases (MASLD), such as Metabolic Associated Fatty Liver Disease and Metabolic Associated Steato Hepatitis, are considered risk factors for HCC. GS may also be involved in the development and progression of hepatocellular carcinoma (HCC) through other signaling pathways, including the rapamycin (mTOR) and Wnt/β-catenin signaling pathways. Furthermore, the correct combination of HSP70, GPC3, and GS can improve the accuracy and precision of HCC diagnosis. However, the prognostic value of GS in different HCC populations remains controversial. The expression of GS affects the sensitivity of HCC cells to radiotherapy and chemotherapy. In addition, immunotherapy has been approved for the treatment of advanced HCC. This article delves into the development and application of GS in HCC, laying a theoretical foundation for the subsequent exploration of GS as a potential target for treating HCC.
谷氨酰胺合成酶（GS）是一种酶，它利用三磷酸腺苷将氨和谷氨酸转化为谷氨酰胺。在正常生理条件下，GS 在脑、肾和肝组织中表达。GS 通过催化谷氨酰胺的从头合成，参与肝脏异常脂质代谢，从而诱导肝脏炎症。代谢相关脂肪性肝病（MASLD），如代谢相关脂肪性肝病和代谢相关脂肪性肝炎，被认为是 HCC 的危险因素。GS 还可能通过雷帕霉素（mTOR）和 Wnt/β-catenin 信号通路等其他信号通路参与肝癌的发生和发展。此外，HSP70、GPC3 和 GS 的正确组合可以提高 HCC 诊断的准确性和精密度。然而，GS 在不同 HCC 人群中的预后价值仍存在争议。GS 的表达影响 HCC 细胞对放疗和化疗的敏感性。此外，免疫疗法已被批准用于治疗晚期 HCC。本文探讨了 GS 在 HCC 中的发展和应用，为后续探索 GS 作为治疗 HCC 的潜在靶点奠定了理论基础。
