Stemness-hypoxia genes PPARGC1A, PFKFB3, and SLC2A5 are associated with prognosis and tumor immune microenvironment in hepatocellular carcinoma.

IF 1.7 4区医学 Q4 ONCOLOGY

Translational cancer research Pub Date : 2025-07-30 Epub Date: 2025-07-25 DOI:10.21037/tcr-24-2030

Dan Wang, Ruotian Wang, Yuewen Zhang, Zhitao Li, Hong Zheng, Wanggang Xu

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引用次数: 0

Abstract

Background: 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.

Methods: 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.

Results: A three-gene prognostic signature based on the stemness-hypoxia genes (PPARGC1A, PFKFB3, and SLC2A5) was constructed. The Kaplan-Meier curve validated the prognostic capacity of the model. PPARGC1A and PFKFB3 were independent prognostic factors for HCC: PPARGC1A expression was significantly associated with favorable overall survival (OS) of HCC patients, while PFKFB3 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, SLC2A5 was significantly up-regulated in HepG2 cells compared to LO-2 cells. Additionally, elevated SLC2A5 expression and reduced PPARGC1A and PFKFB3 expression were observed in both Hep3B and HepG2 cells under hypoxia condition.

Conclusions: 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.

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干细胞-缺氧基因PPARGC1A、PFKFB3和SLC2A5与肝癌的预后和肿瘤免疫微环境相关。

背景：肝细胞癌（HCC）是最常见的肝癌类型。肝癌细胞的干细胞性和缺氧微环境影响肿瘤的进展和抗肿瘤治疗的耐药性。本研究旨在结合肿瘤干性和缺氧特征来评价HCC的预后和肿瘤免疫微环境（TIME）。方法：基于来自the Cancer Genome Atlas （TCGA）数据库的HCC数据，计算基于mRNA表达的干性指数（mRNAsi），获取干性-缺氧基因。采用Cox回归分析，鉴定出与预后相关的干性-缺氧基因，并构建干性-缺氧预后模型。验证了模型的预后能力，并评估了模型与免疫特性之间的关系。此外，我们还检测了缺氧条件下肝癌细胞中模型基因的差异表达。结果：构建了基于干性缺氧基因（PPARGC1A、PFKFB3和SLC2A5）的三基因预后标记。Kaplan-Meier曲线验证了模型的预测能力。PPARGC1A和PFKFB3是HCC的独立预后因素：PPARGC1A表达与HCC患者良好的总生存期（OS）显著相关，而PFKFB3表达与不良的OS相关。此外，高危组与晚期、肿瘤促进免疫细胞浸润和免疫检查点表达升高有关。风险评分也显示出肝癌OS的预后能力和免疫微环境的预测价值。最后，与LO-2细胞相比，SLC2A5在HepG2细胞中显著上调。此外，缺氧条件下Hep3B和HepG2细胞中SLC2A5表达升高，PPARGC1A和PFKFB3表达降低。结论：我们建立的干细胞-缺氧基因标记显示HCC预后良好，且与时间有关。我们的发现为HCC的预后评估提供了新的见解。

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来源期刊

Translational cancer research ONCOLOGY-

CiteScore

2.10

自引率

0.00%

发文量

252

期刊介绍： Translational Cancer Research (Transl Cancer Res TCR; Print ISSN: 2218-676X; Online ISSN 2219-6803; http://tcr.amegroups.com/) is an Open Access, peer-reviewed journal, indexed in Science Citation Index Expanded (SCIE). TCR publishes laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer; results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of cancer patients. The focus of TCR is original, peer-reviewed, science-based research that successfully advances clinical medicine toward the goal of improving patients'' quality of life. The editors and an international advisory group of scientists and clinician-scientists as well as other experts will hold TCR articles to the high-quality standards. We accept Original Articles as well as Review Articles, Editorials and Brief Articles.