Takahara Hirotomo, Kanazawa Takumi, Oshita Haruna, Tomita Yoshinobu, Hananoi Yuri, Ishibashi Sachiko, Ikeda Masumi, Furukawa Asuka, Kinoshita Mayumi, Yamamoto Kurara, Kato Yuki, Ishibashi Hironori, Okubo Kenichi, Kurata Morito, Kitagawa Masanobu, Ohashi Kenichi, Yamamoto Kouhei
Department of Thoracic Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.
Department of Clinical Laboratory Medicine, Faculty of Health Science Technology, Bunkyo Gakuin University, Tokyo 113-8668, Japan.
Cancers (Basel). 2024 Nov 20;16(22):3888. doi: 10.3390/cancers16223888.
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. : 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. : 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. : These findings suggest that lipid peroxidation markers and regulators can serve as prognostic biomarkers and therapeutic targets in lung adenocarcinoma.
原发性肺癌是预后最差的癌症之一，在日本男性癌症死亡率中位居榜首，在女性中位居第二。虽然手术是主要治疗方法，但晚期阶段通常需要药物治疗。最近，铁死亡作为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。本研究调查了脂质过氧化标志物和铁死亡相关调节因子在肺腺癌中的预后影响。：我们分析了207例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-羟基壬烯醛（4-HNE）的表达水平。评估这些标志物与临床病理因素之间的关联，并进行体外实验以检查这些标志物对细胞死亡的影响。：4-HNE的低细胞质积累和GPX4的低表达与较差的预后相关，FSP1的低表达与无复发生存不良相关。体外实验表明，4-HNE抑制细胞增殖，联合抑制GPX4和FSP1可诱导铁死亡。：这些发现表明，脂质过氧化标志物和调节因子可作为肺腺癌的预后生物标志物和治疗靶点。
