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转移素受体与肝细胞癌中对铁灭诱导物的敏感性有关

Maki Hiromatsu¹, Katsuya Toshida¹, Shinji Itoh²

¹Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Annals of surgical oncology

|August 7, 2023

概括

转移素受体 (TFR) 表达表明肝细胞癌 (HCC) 的预后不佳. 然而,TFR水平升高会增加对诱导铁亡的药物的敏感性,这表明TFR在癌症进展和治疗反应中起着双重作用.

科学领域:

在瘤学瘤学.
分子生物学分子生物学
生物化学生物化学

背景情况:

转移素受体 (TFR) 是一种膜蛋白,对细胞铁吸收至关重要,并被认为是与铁亡相关的标记物.
虽然TFR在瘤细胞中经常过度表达,但它在肝细胞癌 (HCC) 中的特定作用和与ferroptosis诱导因子的相关性尚未明确.

研究的目的:

调查TFR表达在HCC中的预后意义.
探索TFR表达和HCC患者的临床病理因素之间的关系.
确定TFR对肝细胞癌细胞恶性瘤的影响以及对铁亡诱导物的敏感性.

主要方法:

在350名HCC患者中对TFR进行了免疫组织化学染色,将他们分为TFR阳性和TFR阴性组.
统计分析评估了TFR表达,预后和临床病理特征之间的关联.
在体外实验中评估了TFRC敲击对HCC细胞运动性和ferroptosis诱导的影响,例如阿尔特苏纳酸 (AS),伦瓦提尼布和索拉芬尼布.

主要成果:

具有TFR阳性的HCC患者 (51.4%) 呈现出明显更多的乙型肝炎表面抗原,更高的AFP和DCP水平,更大的瘤大小,晚期BCLC阶段,差异化和肝脏内转移.
在多变量分析中,TFR表达被确定为较差的无病存活率的独立预后因素.
在体外,TFRC敲击降低了HCC细胞的运动性和废除了AS,lenvatinib和sorafenib诱导的ferroptosis;联合AS和多酶抑制剂治疗增加了ferroptosis.

结论:

TFR表达是肝细胞癌预后不佳的重要指标.
尽管它具有负面的预后作用,但TFR表达增强了HCC细胞对ferroptosis诱导剂的敏感性,突出了复杂的治疗标.

关键词:

铁化是铁化的一种.肝细胞癌是肝细胞癌.伦瓦提尼布 (Lenvatinib) 是一种药物.索拉费尼布 (Sorafenib) 是一种转移氨酸受体的受体转移氨酸受体

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