Shu Qiang, Wang Qiang, Yang Xiaoli, Li Bo
Department of Hepatobiliary Surgery, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China.
Front Immunol. 2025 Apr 7;16:1548691. doi: 10.3389/fimmu.2025.1548691. eCollection 2025.
Ariadne homolog 2 (ARIH2) has been demonstrated to be upregulated in various human cancer tissues. Nevertheless, the underlying biological function of ARIH2 in the progression of hepatocellular carcinoma (HCC) remains ambiguous. Hence, we conducted a comprehensive bioinformatics analysis on the liver hepatocellular carcinoma (LIHC) dataset to explore the role of ARIH2 in tumorigenesis.
The mRNA and protein expression of ARIH2 was analyzed by using data from public databases and verified through immunohistochemical staining and Western blot. Logistic regression, Cox regression, receiver operating characteristic curve (ROC), Kaplan-Meier analysis and nomogram model were employed to assess the association between ARIH2 and the clinicopathological characteristics of HCC. We utilized functional enrichment analysis to investigate the potential pathways of ARIH2 in the progression of HCC. The association of ARIH2 with immune infiltration, ferroptosis and immune checkpoint genes was further evaluated. Finally, the correlation between ARIH2 and the IC50 of chemotherapeutic drugs was analyzed in HCC.
Our study discovered that ARIH2 was up-regulated in HCC tumor tissues compared with the control group. ARIH2 expression could effectively distinguish tumor tissues from normal liver tissues. The genes related to ARIH2 showed differential expression in pathways involving immune system-related pathways and ion channels. We identified a significant association between the expression level of ARIH2 in HCC tissues and immune infiltration, immune checkpoint genes and ferroptosis. The expression level of ARIH2 was significantly correlated with the clinical stage, histological pathological grade and clinical characteristics of HCC, and could independently predict overall survival.
The expression level of ARIH2 may serve as a promising biomarker for the diagnosis and prognosis of HCC, as well as a potential drug target, which holds great significance for the development of targeted therapy for HCC.
已有研究表明，阿里阿德涅同系物2（ARIH2）在多种人类癌症组织中表达上调。然而，ARIH2在肝细胞癌（HCC）进展中的潜在生物学功能仍不明确。因此，我们对肝细胞癌（LIHC）数据集进行了全面的生物信息学分析，以探讨ARIH2在肿瘤发生中的作用。
利用公共数据库的数据对ARIH2的mRNA和蛋白表达进行分析，并通过免疫组织化学染色和蛋白质免疫印迹法进行验证。采用逻辑回归、Cox回归、受试者工作特征曲线（ROC）、Kaplan-Meier分析和列线图模型评估ARIH2与HCC临床病理特征之间的关联。我们利用功能富集分析来研究ARIH2在HCC进展中的潜在途径。进一步评估ARIH2与免疫浸润、铁死亡和免疫检查点基因的关联。最后，分析了ARIH2与HCC中化疗药物IC50之间的相关性。
我们的研究发现，与对照组相比，HCC肿瘤组织中ARIH2表达上调。ARIH2表达可有效区分肿瘤组织与正常肝组织。与ARIH2相关的基因在涉及免疫系统相关途径和离子通道的通路中表现出差异表达。我们发现HCC组织中ARIH2的表达水平与免疫浸润、免疫检查点基因和铁死亡之间存在显著关联。ARIH2的表达水平与HCC的临床分期、组织病理学分级和临床特征显著相关，并可独立预测总生存期。
ARIH2的表达水平可能作为HCC诊断和预后的有前景的生物标志物，以及潜在的药物靶点，这对HCC靶向治疗的发展具有重要意义。
