Feng Zhenxing, Li Bo, Chen Qingliang, Zhang Hong, Guo Zhigang, Qin Jianwen
Department of Radiology, Tianjin Chest Hospital, Tianjin 300222, China.
Department of Cardiovascular Surgery, Tianjin Chest Hospital, Tianjin Cardiovascular Disease Research Institute, Tianjin 300222, China.
J Oncol. 2022 May 17;2022:9054983. doi: 10.1155/2022/9054983. eCollection 2022.
Lung adenocarcinoma (LUAD) is a commonly occurring histological subtype of lung cancer. Glutathione peroxidase 4 (GPX4) is an important regulatory factor of ferroptosis and is involved in the development of many cancers, but its prognostic significance has not been systematically described in LUAD. In this study, we focused on developing a robust GPX4-related prognostic signature (GPS) for LUAD. Data for the training cohort was extracted from The Cancer Genome Atlas, and that for the validation cohort was sourced from the GSE72094 dataset including 863 LUAD patients. GPX4-related genes were screened out by weighted gene coexpression network analysis and Spearman's correlation analysis. Then, Cox regression and least absolute shrinkage and selection operator regression analyses were employed to construct a GPS. The ESTIMATE algorithm, single-sample gene set enrichment analysis (ssGSEA), and GSEA were utilized to evaluate the relationship between GPS and the tumor microenvironment (TME). We constructed and validated a GPS premised on four GPX4-related genes (KIF14, LATS2, PRKCE, and TM6SF1), which could classify LUAD patients into low- and high-score cohorts. The high-risk cohort presented noticeably poorer overall survival (OS) as opposed to the low-risk cohort, meaning that the GPS may be utilized as an independent predictor of the OS of LUAD. The GPS was also adversely correlated with multiple tumor-infiltrating immune cells and immune-related processes and pathways in TME. Furthermore, greater sensitivity to erlotinib and lapatinib were identified in the low-risk cohort based on the GDSC database. Our findings suggest that the GPS can effectively forecast the prognosis of LUAD patients and may possibly regulate the TME of LUAD.
肺腺癌（LUAD）是肺癌中常见的组织学亚型。谷胱甘肽过氧化物酶4（GPX4）是铁死亡的重要调节因子，参与多种癌症的发生发展，但其在LUAD中的预后意义尚未得到系统描述。在本研究中，我们致力于为LUAD开发一种强大的与GPX4相关的预后特征（GPS）。训练队列的数据取自癌症基因组图谱，验证队列的数据来自包含863例LUAD患者的GSE72094数据集。通过加权基因共表达网络分析和Spearman相关性分析筛选出与GPX4相关的基因。然后，采用Cox回归和最小绝对收缩和选择算子回归分析构建GPS。利用ESTIMATE算法、单样本基因集富集分析（ssGSEA）和基因集富集分析（GSEA）评估GPS与肿瘤微环境（TME）之间的关系。我们构建并验证了一个基于四个与GPX4相关基因（KIF14、LATS2、PRKCE和TM6SF1）的GPS，该GPS可将LUAD患者分为低分和高分队列。与低风险队列相比，高风险队列的总生存期（OS）明显更差，这意味着GPS可作为LUAD患者OS的独立预测指标。GPS还与TME中的多种肿瘤浸润免疫细胞以及免疫相关过程和通路呈负相关。此外，基于GDSC数据库，在低风险队列中发现对厄洛替尼和拉帕替尼的敏感性更高。我们的研究结果表明，GPS可以有效地预测LUAD患者的预后，并可能调节LUAD的TME。
