Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.
Department of Biological Repositories, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.
Cell Transplant. 2020 Jan-Dec;29:963689720977131. doi: 10.1177/0963689720977131.
Tumor microenvironment (TME) has critical impacts on the pathogenesis of lung adenocarcinoma (LUAD). However, the molecular mechanism of TME effects on the prognosis of LUAD patients remains unclear. Our study aimed to establish an immune-related gene pair (IRGP) model for prognosis prediction and internal mechanism investigation. Based on 702 TME-related differentially expressed genes (DEGs) extracted from The Cancer Genome Atlas (TCGA) training cohort using the ESTIMATE algorithm, a 10-IRGP signature was established to predict LUAD patient prognosis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses showed that DEGs were significantly associated with tumor immune response. In both TCGA training and Gene Expression Omnibus validation datasets, the risk score was an independent prognostic factor for LUAD patients using Lasso-Cox analysis, and patients in the high-risk group had poorer prognosis than those in the low-risk one. In the high-risk group, M2 macrophage and neutrophil infiltrations were higher, while the levels of T cell follicular helpers were significantly lower. The gene set enrichment analysis results showed that DNA repair signaling pathways were involved. In summary, we established an IRGP signature as a potential biomarker to predict the prognosis of LUAD patients.
肿瘤微环境(TME)对肺腺癌(LUAD)的发病机制有重要影响。然而,TME 对 LUAD 患者预后的影响的分子机制尚不清楚。我们的研究旨在建立一个免疫相关基因对(IRGP)模型,用于预后预测和内部机制研究。基于 ESTIMATE 算法从癌症基因组图谱(TCGA)训练队列中提取的 702 个与 TME 相关的差异表达基因(DEG),建立了一个 10-IRGP 特征来预测 LUAD 患者的预后。基因本体论和京都基因与基因组百科全书分析表明,DEG 与肿瘤免疫反应显著相关。在 TCGA 训练和基因表达综合数据集验证中,Lasso-Cox 分析显示风险评分是 LUAD 患者的独立预后因素,高危组患者的预后比低危组差。在高危组中,M2 巨噬细胞和中性粒细胞浸润更高,而滤泡辅助性 T 细胞水平显著降低。基因集富集分析结果表明,涉及 DNA 修复信号通路。总之,我们建立了一个 IRGP 特征作为预测 LUAD 患者预后的潜在生物标志物。