Xu Maosen, Zhang Yu, Tie Yan, Luo Yiqiao, Wang Yang, Zhang Ziqi
Laboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
Front Endocrinol (Lausanne). 2025 May 29;16:1588529. doi: 10.3389/fendo.2025.1588529. eCollection 2025.
Hepatocellular carcinoma (HCC) is one of the most prevalent and deadly cancers worldwide, with a high recurrence rate and poor prognosis. Understanding the molecular mechanisms driving HCC progression is crucial for improving prognostic accuracy and developing targeted therapies. Bile acids (BAs), as critical regulators of liver metabolism and inflammation, have recently been implicated in tumorigenesis and cancer progression. In particular, bile acids metabolism (BAM)-related genes play a pivotal role in the regulation of cellular proliferation, apoptosis, and immune responses in HCC. In this study, we explored the prognostic significance of BAM-related genes in HCC. Using a comprehensive bioinformatics approach, we analyzed transcriptomic data from public databases, identifying 111 differentially expressed BAM-related genes associated with patient survival. We then constructed a prognostic model based on these key genes, utilizing multivariate Cox regression analysis to determine their independent predictive value for overall survival in HCC patients. We identified four key BAM-related genes including AKR1D1, CYP7A1, FABP6, and NPC1 as significant prognostic markers. Among these genes, only NPC1 was the highly expressed gene and demonstrated statistically difference between HCC and normal liver tissues. The downregulation of NPC1 inhibited HepG2 cell proliferation, migration, and invasion. In conclusion, BAM-related genes offer a promising avenue for improving prognosis assessment in HCC patients. Our findings highlight the potential of NPC1 as a valuable tool for risk stratification and personalized treatment strategies in HCC patients.
肝细胞癌（HCC）是全球最常见且致命的癌症之一，复发率高且预后不良。了解驱动HCC进展的分子机制对于提高预后准确性和开发靶向治疗至关重要。胆汁酸（BAs）作为肝脏代谢和炎症的关键调节因子，最近被认为与肿瘤发生和癌症进展有关。特别是，胆汁酸代谢（BAM）相关基因在HCC的细胞增殖、凋亡和免疫反应调节中起关键作用。在本研究中，我们探讨了BAM相关基因在HCC中的预后意义。使用综合生物信息学方法，我们分析了来自公共数据库的转录组数据，确定了111个与患者生存相关的差异表达BAM相关基因。然后，我们基于这些关键基因构建了一个预后模型，利用多变量Cox回归分析来确定它们对HCC患者总生存的独立预测价值。我们确定了四个关键的BAM相关基因，包括AKR1D1、CYP7A1、FABP6和NPC1，作为显著的预后标志物。在这些基因中，只有NPC1是高表达基因，并且在HCC和正常肝组织之间表现出统计学差异。NPC1的下调抑制了HepG2细胞的增殖、迁移和侵袭。总之，BAM相关基因有望改善HCC患者的预后评估。我们的研究结果突出了NPC1作为HCC患者风险分层和个性化治疗策略的有价值工具的潜力。
