The First Department of Thoracic Medicine, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, 110042, Liaoning, China.
College of Basic Medical Sciences, Dalian Medical University, Dalian, 116044, Liaoning, China.
BMC Pulm Med. 2021 Jul 13;21(1):229. doi: 10.1186/s12890-021-01588-2.
Ferroptosis is a newly discovered form of cell death characterized by iron-dependent lipid peroxidation. This study aims to investigate the potential correlation between ferroptosis and the prognosis of lung adenocarcinoma (LUAD).
RNA-seq data were collected from the LUAD dataset of The Cancer Genome Atlas (TCGA) database. Based on ferroptosis-related genes, differentially expressed genes (DEGs) between LUAD and paracancerous specimens were identified. The univariate Cox regression analysis was performed to screen key genes associated with the prognosis of LUAD. LUAD patients were divided into the training set and validation set. Then, we screened out key genes and built a prognostic prediction model involving 5 genes using the least absolute shrinkage and selection operator (LASSO) regression with tenfold cross-validation and the multivariate Cox regression analysis. After dividing LUAD patients based on the median level of risk score as cut-off value, the generated prognostic prediction model was validated in the validation set. Moreover, we analyzed the somatic mutations, and estimated the scores of immune infiltration in the high-risk and low-risk groups. Functional enrichment analysis of DEGs was performed as well.
High-risk scores indicated the worse prognosis of LUAD. The maximum area under curve (AUC) of the training set and the validation set in this study was 0.7 and 0.69, respectively. Moreover, we integrated the age, gender, and tumor stage to construct the composite nomogram. The charts indicated that the AUC of LUAD cases with the survival time of 1, 3 and 5 years was 0.698, 0.71 and 0.73, respectively. In addition, the mutation frequency of LUAD patients in the high-risk group was significantly higher than that in the low-risk group. Simultaneously, DEGs were mainly enriched in ferroptosis-related pathways by analyzing the functional results.
This study constructs a novel LUAD prognosis prediction model involving 5 ferroptosis-related genes, which can be used as a promising tool for decision-making of clinical therapeutic strategies of LUAD.
铁死亡是一种新发现的细胞死亡形式，其特征是铁依赖性脂质过氧化。本研究旨在探讨铁死亡与肺腺癌（LUAD）预后之间的潜在相关性。
从癌症基因组图谱（TCGA）数据库的 LUAD 数据集收集 RNA-seq 数据。基于铁死亡相关基因，鉴定 LUAD 与癌旁标本之间的差异表达基因（DEGs）。进行单变量 Cox 回归分析，筛选与 LUAD 预后相关的关键基因。将 LUAD 患者分为训练集和验证集。然后，我们使用十折交叉验证和多变量 Cox 回归分析的最小绝对收缩和选择算子（LASSO）回归筛选出关键基因，并构建了一个涉及 5 个基因的预后预测模型。根据风险评分中位数作为截断值将 LUAD 患者分为高风险和低风险组后，在验证集验证生成的预后预测模型。此外，我们还分析了体细胞突变，并估计了高风险和低风险组的免疫浸润评分。同时，还对 DEGs 进行了功能富集分析。
高风险评分表明 LUAD 的预后较差。本研究中训练集和验证集的最大曲线下面积（AUC）分别为 0.7 和 0.69。此外，我们整合了年龄、性别和肿瘤分期来构建综合列线图。该图表表明，生存时间为 1、3 和 5 年的 LUAD 患者的 AUC 分别为 0.698、0.71 和 0.73。此外，高风险组 LUAD 患者的突变频率明显高于低风险组。同时，通过分析功能结果，发现 DEGs 主要富集在铁死亡相关途径中。
本研究构建了一个涉及 5 个铁死亡相关基因的 LUAD 预后预测模型，可作为 LUAD 临床治疗策略决策的有前途的工具。
