Cui Yao, Zhang Lu-Jin, Xu Yu-Jie, Liu Ming-Yue
Department of Oncology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Henan University People's Hospital Zhengzhou 450003, Henan, China.
Am J Transl Res. 2023 Jun 15;15(6):3942-3959. eCollection 2023.
Lung adenocarcinoma (LUAD) is the leading histological subtype of lung cancer worldwide, causing high annual mortality. Tsvetkov et al. recently found a new form of regulated cell death, termed cuproptosis. The prognostic value of cuproptosis-related gene signature in LUAD remains uncertain.
A training cohort is identified by the TCGA-LUAD dataset, whereas validation cohorts one and two are identified by GSE72094 and GSE68465, respectively. GeneCard and GSEA were used to extract genes related to cuproptosis. Cox regression, Kaplan-Meier regression, and LASSO regression were used to construct a gene signature. The model's applicability was evaluated by Kaplan-Meier estimators, Cox models, ROC, and tAUC across two independent validation cohorts. We examined the model's connections with other forms of regulated cell death. The immunotherapy ability of the signature was demonstrated by applying TMB, immune relevant signatures, and TIDE. The GSEA and immune infiltration analysis offer a better understanding of how the signature functions and the role of immune cells in its prognostic power.
A ten-gene signature was built and demonstrated owning prognostic power by being applied to the validation cohorts. The GSEA uncovered that the unfolded protein response, glycolysis/gluconeogenesis, and MYC were highly related to the gene signature. The ten-gene signature is closely related to related genes of apoptosis, necroptosis, pyroptosis, and ferroptosis. Our signature may have utility in predicting immunotherapy efficacy in LUADs. Mast cells were identified as key players that support the predicting capacity of the ten-gene signature through the immune infiltrating analysis.
The novel ten-gene signature associated with apoptosis in cuproptosis that we obtained may contribute to improved LUAD management strategies and the ability to predict response to LUAD immunotherapy. It is suggested that mast cell infiltration might be related to the prognostic power of this signature.
肺腺癌（LUAD）是全球肺癌中主要的组织学亚型，每年导致的死亡率很高。Tsvetkov等人最近发现了一种新的程序性细胞死亡形式，称为铜死亡。铜死亡相关基因特征在LUAD中的预后价值仍不确定。
通过TCGA-LUAD数据集确定一个训练队列，而验证队列一和队列二则分别通过GSE72094和GSE68465确定。使用GeneCard和GSEA来提取与铜死亡相关的基因。采用Cox回归、Kaplan-Meier回归和LASSO回归构建基因特征。通过Kaplan-Meier估计器、Cox模型、ROC和tAUC在两个独立的验证队列中评估该模型的适用性。我们研究了该模型与其他形式程序性细胞死亡的联系。通过应用TMB、免疫相关特征和TIDE证明了该特征的免疫治疗能力。GSEA和免疫浸润分析有助于更好地理解该特征的作用机制以及免疫细胞在其预后能力中的作用。
构建了一个包含十个基因的特征，并通过应用于验证队列证明了其具有预后能力。GSEA发现未折叠蛋白反应、糖酵解/糖异生和MYC与该基因特征高度相关。这十个基因的特征与凋亡、坏死性凋亡、细胞焦亡和铁死亡的相关基因密切相关。我们的特征可能有助于预测LUAD的免疫治疗疗效。通过免疫浸润分析确定肥大细胞是支持十个基因特征预测能力的关键因素。
我们获得的与铜死亡中凋亡相关的新型十个基因特征可能有助于改进LUAD的管理策略以及预测LUAD免疫治疗反应的能力。提示肥大细胞浸润可能与该特征的预后能力有关。
