Background:Primary lung cancer is among the cancers with the poorest prognosis, having the highest mortality rate among men and the second highest among women in Japan. While surgery is the primary treatment, advanced stages often require pharmacotherapy. Recently, ferroptosis, an iron-dependent form of cell death caused by lipid peroxidation, has gained attention as a potential therapeutic strategy. This study investigated the prognostic impact of lipid peroxidation marker and regulators involved in ferroptosis in lung adenocarcinoma.Methods: We analyzed 207 patients who underwent resection surgery for lung adenocarcinoma at Tokyo Medical and Dental University Hospital. Immunohistochemistry was used to evaluate the expression levels of glutathione peroxidase 4 (GPX4), ferroptosis suppressor protein 1 (FSP1), and 4-hydroxy-2-nonenal (4-HNE). The association between these markers and clinicopathological factors was assessed, and in vitro experiments were conducted to examine the effects of these markers on cell death.Results: Low cytoplasmic accumulation of 4-HNE and low expression of GPX4 were associated with a worse prognosis, and low FSP1 expression was associated with unfavorable relapse-free survival. In vitro experiments demonstrated that 4-HNE inhibited cell proliferation, and combined inhibition of GPX4 and FSP1 induced ferroptosis.Conclusions: These findings suggest that lipid peroxidation markers and regulators can serve as prognostic biomarkers and therapeutic targets in lung adenocarcinoma.
背景：原发性肺癌是预后最差的癌症之一，在日本男性中死亡率最高，在女性中死亡率位居第二。虽然手术是主要治疗手段，但晚期患者通常需要药物治疗。近年来，铁死亡——一种由脂质过氧化引起的铁依赖性细胞死亡形式——作为一种潜在的治疗策略受到关注。本研究探讨了脂质过氧化标志物及铁死亡相关调控因子在肺腺癌中的预后影响。 方法：我们分析了207名在东京医科齿科大学医院接受肺腺癌切除手术的患者。采用免疫组织化学方法评估谷胱甘肽过氧化物酶4（GPX4）、铁死亡抑制蛋白1（FSP1）和4-羟基-2-壬烯醛（4-HNE）的表达水平。评估了这些标志物与临床病理因素之间的关联，并通过体外实验检测了这些标志物对细胞死亡的影响。 结果：4-HNE的低细胞质积累和GPX4的低表达与较差的预后相关，而FSP1的低表达与不良的无复发生存期相关。体外实验表明，4-HNE抑制细胞增殖，而联合抑制GPX4和FSP1可诱导铁死亡。 结论：这些发现表明，脂质过氧化标志物及其调控因子可作为肺腺癌的预后生物标志物和治疗靶点。
肿瘤(癌症)患者之家