铁死亡的本质是铁增加导致膜脂质过氧化物的积累，破坏细胞内的氧化还原平衡并引发细胞死亡。铁代谢异常会显着增加患肺癌的风险并诱发治疗抵抗。然而，吸烟在肺癌患者铁死亡中的作用和机制仍不清楚。我们的研究是二次生物信息学分析，随后是实验性细胞培养分析。在这项研究中，我们基于癌症基因组图谱 (TCGA) 数据库，鉴定了不同的铁死亡相关基因，并在不同吸烟状态的肺鳞状细胞癌 (LUSC) 和肺腺癌 (LUAD) 患者中建立了特征。 LUSC患者中的范酰二磷酸范酰转移酶1（FDFT1）和LUAD患者中的溶质载体一家族成员5（SLC1A5）被证实与铁死亡相关。接下来，我们检查了烟雾的两种主要成分尼古丁和苯并（a）芘（BaP）在非小细胞肺癌（NSCLC）细胞铁死亡中的作用。我们证实尼古丁抑制活性氧（ROS） ) 水平并诱导谷胱甘肽过氧化物酶 (GPX4) 表达，而在 NSCLC 细胞中观察到 BaP 的相反作用。从机械角度来说，尼古丁通过上调表皮生长因子受体 (EGFR) 和 SLC1A5 的表达来保护 NSCLC 细胞免于铁死亡。 BaP 诱导的 NSCLC 细胞铁死亡依赖于 FDFT1 表达。在本研究中，在不同吸烟状态的 LUAD 和 LUSC 患者中鉴定了铁死亡相关基因特征。我们通过上调 EGFR 和 SLC1A5 表达证实尼古丁保护 LUAD 和 LUSC 细胞免于铁死亡。 BaP 在这些细胞中诱导的铁死亡取决于 FDFT1 表达。© 2024 Wen M.G.等人。

The essence of ferroptosis is the accumulation of membrane lipid peroxides caused by increased iron, which disrupts the redox balance within cells and triggers cell death. Abnormal metabolism of iron significantly increases the risk of lung cancer and induces treatment resistance. However, the roles and mechanisms of smocking in ferroptosis in patients with lung cancer are still unclear.Our study was a secondary bioinformatics analysis followed by an experimental cell culture analysis. In this study, we identified the different ferroptosis-related genes and established the signature in lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) patients with different smocking status, based on The Cancer Genome Atlas (TCGA) database. Fanyl diphosphate fanyl transferase 1 (FDFT1) in LUSC patients and solute carrier one family member 5 (SLC1A5) in LUAD patients were confirmed to be related to ferroptosis. Next, we checked the roles of two main components of smoke, nicotine, and benzo(a)pyrene (BaP), in ferroptosis of non-small-cell lung cancer (NSCLC) cells.We confirmed that nicotine inhibited reactive oxygen species (ROS) levels and induced glutathione peroxidase (GPX4) expression, while the opposite roles of BaP were observed in NSCLC cells. Mechanically, nicotine protected NSCLC cells from ferroptosis through upregulation of epidermal growth factor receptor (EGFR) and SLC1A5 expression. BaP-induced ferroptosis in NSCLC cells depends on FDFT1 expression.In this study, the ferroptosis-associated gene signature was identified in LUAD and LUSC patients with different smoking status. We confirmed nicotine-protected LUAD and LUSC cells from ferroptosis by upregulating EGFR and SLC1A5 expression. BaP-induced ferroptosis in these cells depends on FDFT1 expression.© 2024 Wen M.G. et al.