Luo Lianxiang, Zhang Zhentao, Weng Yanmin, Zeng Jiayan
The Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang 524023, China.
The Marine Biomedical Research Institute of Guangdong Zhanjiang, Zhanjiang 524023, China.
Cells. 2022 Oct 25;11(21):3371. doi: 10.3390/cells11213371.
Ferroptosis, a newly discovered iron-dependent type of cell death, has been found to play a crucial role in the depression of tumorigenesis. However, the prognostic value of ferroptosis-related genes (FRGs) in lung adenocarcinoma (LUAD) remains to be further elucidated. Differential expression analysis and univariate Cox regression analysis were utilized in this study to search for FRGs that were associated with the prognosis of LUAD patients. The influences of candidate markers on LUAD cell proliferation, migration, and ferroptosis were evaluated by CCK8, colony formation, and functional experimental assays in association with ferroptosis. To predict the prognosis of LUAD patients, we constructed a predictive signature comprised of six FRGs. We discovered a critical gene (GCLC) after intersecting the prognostic analysis results of all aspects, and its high expression was associated with a bad prognosis in LUAD. Correlation research revealed that GCLC was related to a variety of clinical information from LUAD patients. At the same time, in the experimental verification, we found that GCLC expression was upregulated in LUAD cell lines, and silencing GCLC accelerated ferroptosis and decreased LUAD cell proliferation and invasion. Taken together, this study established a novel ferroptosis-related gene signature and discovered a crucial gene, GCLC, that might be a new prognostic biomarker of LUAD patients, as well as provide a potential therapeutic target for LUAD patients.
铁死亡是一种新发现的铁依赖性细胞死亡类型，已被发现对肿瘤发生的抑制起着关键作用。然而，铁死亡相关基因（FRGs）在肺腺癌（LUAD）中的预后价值仍有待进一步阐明。本研究利用差异表达分析和单因素Cox回归分析来寻找与LUAD患者预后相关的FRGs。通过CCK8、集落形成以及与铁死亡相关的功能实验分析，评估候选标志物对LUAD细胞增殖、迁移和铁死亡的影响。为了预测LUAD患者的预后，我们构建了一个由六个FRGs组成的预测特征。在综合各方面预后分析结果后，我们发现了一个关键基因（GCLC），其高表达与LUAD患者的不良预后相关。相关性研究表明，GCLC与LUAD患者的多种临床信息有关。同时，在实验验证中，我们发现GCLC在LUAD细胞系中表达上调，沉默GCLC可加速铁死亡并降低LUAD细胞的增殖和侵袭。综上所述，本研究建立了一种新的铁死亡相关基因特征，并发现了一个关键基因GCLC，它可能是LUAD患者新的预后生物标志物，也为LUAD患者提供了潜在的治疗靶点。
