Wang Dan, Wang Ruotian, Zhang Yuewen, Li Zhitao, Zheng Hong, Xu Wanggang
Department of Transplantation, the First Affiliated Hospital of Kunming Medical University, Kunming, China.
Department of General Surgery, Yan'an Hospital Affiliated to Kunming Medical University, Kunming, China.
Transl Cancer Res. 2025 Jul 30;14(7):4009-4023. doi: 10.21037/tcr-24-2030. Epub 2025 Jul 25.
Hepatocellular carcinoma (HCC) is the most common type of liver cancer. The stemness of cancer cells and hypoxic microenvironment in HCC influence tumor progression and resistance to anti-tumor therapies. Herein, we aimed to combine tumoral stemness and hypoxia features to evaluate the prognosis and tumor immune microenvironment (TIME) in HCC.
Based on the HCC data from The Cancer Genome Atlas (TCGA) database, the mRNA expression-based stemness index (mRNAsi) was calculated, followed by acquisition of stemness-hypoxia genes. The prognostic stemness-hypoxia genes were identified using Cox regression analysis and a stemness-hypoxia prognostic model was constructed. The prognostic capacity of the model was validated, and the associations between the model and immune characteristics were evaluated. Moreover, the differential expression of model genes in HCC cells under hypoxia condition was determined.
A three-gene prognostic signature based on the stemness-hypoxia genes (, , and ) was constructed. The Kaplan-Meier curve validated the prognostic capacity of the model. and were independent prognostic factors for HCC: expression was significantly associated with favorable overall survival (OS) of HCC patients, while expression was related to poor OS. Furthermore, the high-risk group was associated with advanced stages, infiltrated tumor-promoting immune cells, and elevated expression of immune checkpoints. The risk score also exhibited prognostic capacity for the OS and predictive value for the immune microenvironment in HCC. Finally, was significantly up-regulated in HepG2 cells compared to LO-2 cells. Additionally, elevated expression and reduced and expression were observed in both Hep3B and HepG2 cells under hypoxia condition.
Our established stemness-hypoxia gene signature showed favorable prognosis performance for HCC and was related to TIME. Our findings provide novel insights into the prognostic evaluation of HCC.
肝细胞癌（HCC）是最常见的肝癌类型。HCC中癌细胞的干性和缺氧微环境影响肿瘤进展及对抗肿瘤治疗的耐药性。在此，我们旨在结合肿瘤干性和缺氧特征来评估HCC的预后及肿瘤免疫微环境（TIME）。
基于来自癌症基因组图谱（TCGA）数据库的HCC数据，计算基于mRNA表达的干性指数（mRNAsi），随后获取干性-缺氧基因。使用Cox回归分析鉴定预后干性-缺氧基因，并构建干性-缺氧预后模型。验证该模型的预后能力，并评估模型与免疫特征之间的关联。此外，确定缺氧条件下HCC细胞中模型基因的差异表达。
构建了基于干性-缺氧基因（ 、 和 ）的三基因预后特征。Kaplan-Meier曲线验证了模型的预后能力。 和 是HCC的独立预后因素： 表达与HCC患者良好的总生存期（OS）显著相关，而 表达与不良OS相关。此外，高危组与晚期、浸润性促肿瘤免疫细胞以及免疫检查点表达升高相关。风险评分对HCC的OS也具有预后能力，并对免疫微环境具有预测价值。最后，与LO-2细胞相比，HepG2细胞中 显著上调。此外，在缺氧条件下，Hep3B和HepG2细胞中均观察到 表达升高， 及 表达降低。
我们建立的干性-缺氧基因特征对HCC显示出良好的预后性能，并且与TIME相关。我们的研究结果为HCC的预后评估提供了新的见解。
