转铁蛋白受体（TFR）是一种在细胞内铁运输中起重要作用的膜蛋白，被认为是与铁死亡相关的标记物。尽管已有报道称TFR在肿瘤细胞中表达丰度较高，但其与肝细胞癌（HCC）中的铁死亡诱导剂之间的关系尚不清楚。作者对350例HCC患者进行了TFR的免疫组化染色，并根据其表达将其分为两组。分析了TFR表达与预后或临床病理因素之间的关联。此外，还在体外研究了恶性活性的调控以及对铁死亡诱导剂疗效的影响。 本研究共有350名患者被分为TFR阳性组（n =180, 51.4%）和TFR阴性组（n = 170, 48.6%）。TFR阳性组中乙型肝炎表面抗原（HBs-Ag）的比例较高（p = 0.0230），α-胎蛋白（AFP）水平较高（p = 0.0023），脱伽马羧基凝血酮（DCP）水平较高（p = 0.0327），肿瘤大小较大（p = 0.0090），巴塞罗那肝癌临床分期（BCLC）为B或C期的比例较高（p = 0.0005），分化程度较差（p < 0.0001），且有显微镜下肝内转移（p = 0.0066）。多变量分析结果显示TFR表达是无病生存的独立预后因素（p = 0.0315）。体外实验中，TFRC基因沉默抑制了细胞运动能力。此外，TFRC基因沉默使艾草素（AS）、来那度胺和索拉非尼诱导的HCC细胞铁死亡作用消失。该研究证明了在HCC细胞系中，同时应用AS和多激酶抑制剂能增强AS的铁死亡诱导效果。 TFR的表达是HCC的不良预后因素，但其表达增加了对铁死亡诱导剂的敏感性。©2023年。外科肿瘤学学会。

Transferrin receptor (TFR), a membrane protein that has a critical role in the transport of iron into cells, is known to be a ferroptosis-related marker. Although TFR is reported to be abundantly expressed in tumor cells, its relationship with ferroptosis inducers in hepatocellular carcinoma (HCC) remains unclear.The authors performed immunohistochemical staining of TFR and divided 350 HCC patients into two groups according to its expression. They analyzed the association between TFR expression and prognosis or clinicopathologic factors. In addition, the regulation of malignant activity and its effect on the efficacy of ferroptosis inducers were investigated in vitro.For this study, 350 patients were divided into TFR-positive (n =180, 51.4%) and TFR-negative (n = 170, 48.6%) groups. The TFR-positive group had more hepatitis B surface antigen (HBs-Ag) (p = 0.0230), higher α-fetoprotein (AFP) levels (p = 0.0023), higher des-gamma-carboxyprothrombin (DCP) levels (p = 0.0327), a larger tumor size (p = 0.0090), greater proportions of Barcelona Clinic Liver Cancer (BCLC) stage B or C (p = 0.0005), poor differentiation (p < 0.0001), and microscopic intrahepatic metastasis (p = 0.0066). In the multivariate analyses, TFR expression was an independent prognostic factor in disease-free survival (p = 0.0315). In vitro, TFRC knockdown decreased cell motility. In addition, TFRC knockdown abolished artesunate (AS)-, lenvatinib-, and sorafenib-induced ferroptosis in HCC cell lines. The study demonstrated that simultaneous treatment of AS with multi-kinase inhibitor augmented the ferroptosis-inducing effects of AS in HCC cell lines.TFR expression is a poor prognostic factor in HCC, but its expression increases sensitivity to ferroptosis-inducing agents.© 2023. Society of Surgical Oncology.