Department of Hepatobiliary Surgery, The First Hospital of Putian City, Putian, Fujian 351100, P.R. China.
Department of Hepatobiliary Surgery, The First Hospital of Putian City, Putian, Fujian 351100, P.R. China; Department of Clinical Medicine, Fujian Medical University, Fuzhou, Fujian 350122, P.R. China.
J Environ Pathol Toxicol Oncol. 2024;43(4):25-42. doi: 10.1615/JEnvironPatholToxicolOncol.2024049848.
Inferferon-gamma (LFN-γ) exerts anti-tumor effects, but there is currently no reliable and comprehensive study on prognostic function of IFN-γ-related genes in liver cancer. In this study, IFN-γ-related differentially expressed genes (DEGs) in liver cancer were identified through GO/KEGG databases and open-access literature. Based on these genes, individuals with liver cancer were clustered. A prognostic model was built based on the intersection genes between differential genes in clusters and in liver cancer. Then, model predictive performance was analyzed and validated in GEO dataset. Regression analysis was fulfilled on the model, and a nomogram was utilized to evaluate model ability as an independent prognostic factor and its clinical application value. An immune-related analysis was conducted on both the H- and L-groups, with an additional investigation into link of model genes to drug sensitivity. Significant differential expression of IFN-γ-related genes was observed between the liver cancer and control groups. Subsequently, individuals with liver cancer were classified into two subtypes based on these genes, which displayed a notable difference in survival between the two subtypes. A 10-gene liver cancer prognostic model was constructed, with good prognostic performance and was an independent prognosticator for patient analysis. L-group patients possessed higher immune infiltration levels, immune checkpoint expression levels, and immunophenoscore, as well as lower TIDE scores. Drugs that had high correlations with the feature genes included SPANXB1: PF-04217903, SGX-523, MMP1: PF-04217903, DUSP13: Imatinib, TFF1: KHK-Indazole, and Fulvestrant. We built a 10-gene liver cancer prognostic model. It was found that L-group patients were more suitable for immunotherapy. This study provided valuable information on the prognosis of liver cancer.
干扰素-γ(IFN-γ)具有抗肿瘤作用,但目前尚无关于 IFN-γ相关基因在肝癌中预后功能的可靠和全面的研究。本研究通过 GO/KEGG 数据库和开放获取文献确定了肝癌中 IFN-γ相关差异表达基因(DEGs)。基于这些基因,对肝癌患者进行聚类。基于聚类和肝癌中差异基因的交集基因构建预后模型。然后,在 GEO 数据集上分析和验证模型预测性能。对模型进行回归分析,并利用列线图评估模型作为独立预后因素的能力及其临床应用价值。对 H-和 L-两组进行免疫相关分析,并进一步研究模型基因与药物敏感性的关系。在肝癌和对照组之间观察到 IFN-γ相关基因的显著差异表达。随后,基于这些基因将肝癌患者分为两种亚型,两种亚型的生存差异显著。构建了一个包含 10 个基因的肝癌预后模型,该模型具有良好的预后性能,是患者分析的独立预后因素。L-组患者具有更高的免疫浸润水平、免疫检查点表达水平和免疫表型评分,以及更低的 TIDE 评分。与特征基因具有高相关性的药物包括 SPANXB1:PF-04217903、SGX-523、MMP1:PF-04217903、DUSP13:伊马替尼、TFF1:KHK-Indazole 和氟维司群。我们构建了一个包含 10 个基因的肝癌预后模型。发现 L-组患者更适合免疫治疗。本研究为肝癌的预后提供了有价值的信息。