Zhang Xiaorong, Zhong Yifan, Yang Qing
Department of Pathogenobiology, College of Basic Medical Sciences, Jilin University, Changchun, 130021, Jilin Province, China.
Cell Biochem Biophys. 2024 Sep;82(3):2767-2785. doi: 10.1007/s12013-024-01393-8. Epub 2024 Jul 20.
Hepatocellular carcinoma (HCC) presents significant challenges in treatment and prognosis because of its aggressive nature and high metastatic potential. This study aims to investigate the role of the hexosamine biosynthesis pathway (HBP) and its association with HCC progression and prognosis. We identified SPP1 and FOXM1 as hub genes within the HBP pathway, showing their correlation with poor prognosis and late-stage progression. In addition, the analysis uncovered the complex participation of the HBP pathway in nutrients and oxygen reactions, PI3K-AKT signaling, AMPK activation, and angiogenesis regulation. The disruption of these pathways is pivotal in influencing the growth and progression of HCC. Targeting the HBP presents a promising therapeutic approach to modulate the tumor microenvironment, thereby enhancing the efficacy of immunotherapy. In addition, FOXM1 was identified as the HBP pathway regulator, influencing cellular O-GlcNAcylation level and VEGF secretion, thereby promoting angiogenesis in HCC. Inhibition of O-GlcNAcylation significantly hindered angiogenesis, which is suggested as a potential avenue for therapeutic intervention. Our research demonstrates the practicality of using the HBP-related gene as a prognostic marker in liver cancer patients and suggests targeting FOXM1 as a novel avenue for personalized therapy.
肝细胞癌（HCC）因其侵袭性本质和高转移潜能，在治疗和预后方面面临重大挑战。本研究旨在探讨己糖胺生物合成途径（HBP）的作用及其与HCC进展和预后的关联。我们确定SPP1和FOXM1为HBP途径中的关键基因，显示它们与不良预后和晚期进展相关。此外，分析揭示了HBP途径在营养物质和氧气反应、PI3K - AKT信号传导、AMPK激活及血管生成调节中的复杂参与。这些途径的破坏在影响HCC的生长和进展中起关键作用。靶向HBP是一种有前景的治疗方法，可调节肿瘤微环境，从而提高免疫治疗的疗效。此外，FOXM1被确定为HBP途径调节剂，影响细胞O - GlcNAcylation水平和VEGF分泌，从而促进HCC中的血管生成。抑制O - GlcNAcylation显著阻碍血管生成，这被认为是一种潜在的治疗干预途径。我们的研究证明了使用HBP相关基因作为肝癌患者预后标志物的实用性，并建议靶向FOXM1作为个性化治疗的新途径。
