Department of Surgery, Division of Gastrointestinal and Pediatric Surgery, Faculty of Medicine, Tottori University, Yonago, Japan.
Department of Surgery, Division of Gastrointestinal and Pediatric Surgery, Faculty of Medicine, Tottori University, Yonago, Japan;
Anticancer Res. 2024 Nov;44(11):4905-4914. doi: 10.21873/anticanres.17316.
BACKGROUND/AIM: Ferroptosis is a nonapoptotic type of cell death that is dependent on iron and involves the accumulation of reactive oxygen species. Ferroptosis suppressor protein 1 (FSP1) and glutathione peroxidase 4 (GPX4) are ferroptosis regulators that inhibit ferroptosis through independent pathways. This study assessed the prognostic value of GPX4 and FSP1 expression in colorectal cancer (CRC). We also examined the effects of FSP1 and GPX4 inhibition on cell survival of CRC cells.
This study included 206 surgical specimens from Stage II or III CRC patients. FSP1 and GPX4 expression was analyzed immunohistochemically, and the association of their expression levels with clinical outcome was evaluated. We also examined the effects of FSP1 and GPX4 inhibitors on the cell proliferative capacity of CRC cell lines.
Overall survival and recurrence-free survival were reduced in patients with high expression of FSP1 or GPX4, and those with both GPX4 and FSP1 expression showed worse prognosis. Positivity of both FSP1 and GPX4 was an independent poor prognostic factor for CRC patients. In CRC cells, the combination of GPX4 and FSP1 inhibitors led to more effective cell death than either inhibitor alone.
High expression of both GPX4 and FSP1 is a significant poor prognostic factor for CRC. Simultaneous inhibition of GPX4 and FSP1 to induce ferroptosis may be a novel therapeutic strategy in CRC.
背景/目的：铁死亡是一种依赖于铁且涉及活性氧物种积累的非细胞凋亡型细胞死亡。铁死亡抑制蛋白 1（FSP1）和谷胱甘肽过氧化物酶 4（GPX4）是铁死亡调节因子，它们通过独立途径抑制铁死亡。本研究评估了 GPX4 和 FSP1 在结直肠癌（CRC）中的表达的预后价值。我们还研究了 FSP1 和 GPX4 抑制对 CRC 细胞存活的影响。
本研究纳入了 206 例 II 期或 III 期 CRC 手术标本。采用免疫组织化学法分析 FSP1 和 GPX4 的表达，并评估其表达水平与临床结局的相关性。我们还研究了 FSP1 和 GPX4 抑制剂对 CRC 细胞系增殖能力的影响。
FSP1 或 GPX4 高表达的患者总生存和无复发生存率降低，同时表达 GPX4 和 FSP1 的患者预后更差。FSP1 和 GPX4 均阳性是 CRC 患者的独立不良预后因素。在 CRC 细胞中，GPX4 和 FSP1 抑制剂的联合使用导致比单独使用任一抑制剂更有效的细胞死亡。
GPX4 和 FSP1 的高表达是 CRC 的一个显著不良预后因素。同时抑制 GPX4 和 FSP1 以诱导铁死亡可能是 CRC 的一种新的治疗策略。
