Department of Oncology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
The Second Clinical Medical College, Wenzhou Medical University, Wenzhou, China.
J Clin Lab Anal. 2021 Dec;35(12):e24086. doi: 10.1002/jcla.24086. Epub 2021 Nov 9.
Ferroptosis is an iron-dependent programmed cell death mechanism that influences the development of malignancy. Lung adenocarcinoma (LUAD) is the most common type of lung cancer with no known cure. Anti-PD-1/PD-L immunotherapy is effective for patients with partial LUAD. Therefore, there is an immediate requirement of novel markers to predict the individualised benefits of immunotherapy.
We manually collected the ferroptosis-related gene (FERG) set and employed the Wilcoxon rank-sum test to identify the differentially expressed FERGs. Subsequently, we constructed a recursive partitioning and regression tree (RPART) model to predict the benefits of anti-PD-1/PD-L1 immunotherapy. Subsequently, the ROC curve and AUC were used to evaluate the model efficiency in an independent dataset.
In this study, we found that the dysregulated FERGs were closely associated with multiple metabolic processes in LUAD. Furthermore, we identified three ferroptosis-related tumour subtypes (F1, F3 and F3). The F3 subtype exhibited higher immunoactivity and lower tumour purity, mutation count and aneuploidy and had better survival outcomes compared with the other two subtypes, implying that FERGs played an important role in intertumoral immune heterogeneity. We further explored the role of FERGs in the anti-PD-1/PD-L1 immunotherapy. We identified a set of three-FERGs signature (CD44, G6PD and ZEB1) that acted as a promising indicator (AUC = 0.697) for the prediction of the benefits of anti-PD-1/PD-L1 immunotherapy.
Ferroptosis, as emerging programmed cell death mechanism, was associated with cancer development. We used ferroptosis-related genes to predict the immunotherapy benefits that may facilitate the development of individualised anti-cancer treatment strategies.
铁死亡是一种依赖铁的程序性细胞死亡机制，影响恶性肿瘤的发展。肺腺癌（LUAD）是最常见的肺癌类型，目前尚无已知的治愈方法。抗 PD-1/PD-L1 免疫疗法对部分 LUAD 患者有效。因此，迫切需要新的标志物来预测免疫治疗的个体化获益。
我们手动收集了铁死亡相关基因（FERG）集，并采用 Wilcoxon 秩和检验来鉴定差异表达的 FERGs。随后，我们构建了递归分区和回归树（RPART）模型来预测抗 PD-1/PD-L1 免疫治疗的获益。随后，我们在独立数据集上使用 ROC 曲线和 AUC 来评估模型的效率。
在这项研究中，我们发现失调的 FERGs 与 LUAD 中的多种代谢过程密切相关。此外，我们鉴定了三种铁死亡相关的肿瘤亚型（F1、F3 和 F3）。与其他两种亚型相比，F3 亚型表现出更高的免疫活性和更低的肿瘤纯度、突变计数和非整倍性，并且具有更好的生存结局，这表明 FERGs 在肿瘤间免疫异质性中发挥着重要作用。我们进一步探讨了 FERGs 在抗 PD-1/PD-L1 免疫治疗中的作用。我们鉴定了一组三个 FERGs 特征（CD44、G6PD 和 ZEB1），作为预测抗 PD-1/PD-L1 免疫治疗获益的有前途的指标（AUC=0.697）。
铁死亡作为一种新兴的程序性细胞死亡机制，与癌症的发生发展有关。我们使用铁死亡相关基因来预测免疫治疗的获益，这可能有助于制定个体化的抗癌治疗策略。
