Screening and evaluation of the role of immune genes of brain metastasis in lung adenocarcinoma progression based on the TCGA and GEO databases.
Screening and evaluation of the role of immune genes of brain metastasis in lung adenocarcinoma progression based on the TCGA and GEO databases.
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DOI：
10.21037/jtd-21-935
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发表时间：
2021-08
影响因子：
2.5
通讯作者：
Song Y
中科院分区：
文献类型：
--
作者：
Chen C;Guo Q;Tang Y;Qu W;Zuo J;Ke X;Song Y
脑转移是导致肺腺癌（LUAD）患者长期预后不良的因素之一。利用GEO2R分析GSE161116数据集中LUAD和LUAD脑转移组织中免疫基因的表达水平，并验证正常肺组织和LUAD组织中差异免疫基因的表达水平。通过《基因本体》和《京都基因与基因组百科全书》对差异免疫基因的生物学功能和信号传导机制进行了探讨。采用Cox回归分析筛选影响LUAD患者预后的因素，构建风险模型。通过受体操作特征分析、基因集富集分析和Cox回归分析，验证了该模型在LUAD发展中的作用。脑转移中的差异表达基因（DEGs）参与了适应性免疫反应、B细胞分化、白细胞迁移、NF-kB信号通路等。Cox回归分析和Akaike信息标准显示，TNFRSF11A、MS4A2、IL11、CAMP、MS4A1、F2RL1的表达水平是影响LUAD患者预后不良的独立因素。在构建的风险模型中，高危组LUAD患者的总生存率较差。风险模型与LUAD患者的性别、临床分期、T分期、淋巴结转移、生存状况有显著相关。此外，风险模型评分是影响LUAD患者预后不良的独立危险因素。TNFRSF11A、CAMP、F2RL1、IL11、MS4A1、MS4A2等危险因素在LUAD脑转移及LUAD中具有诊断意义。风险模型参与细胞动力学过程、细胞周期、柠檬酸循环、TCA循环等。风险模型评分与B细胞记忆、肥大细胞静息、巨噬细胞M0、肥大细胞活化、中性粒细胞、嗜酸性粒细胞、T细胞γ δ和免疫细胞标志物的水平相关。基于LUAD脑转移免疫因子TNFRSF11A、MS4A2、IL11、CAMP、MS4A1、F2RL1的风险模型与LUAD患者的诊断、预后不良、免疫浸润细胞相关，有望为LUAD患者治疗策略的制定提供参考。
Brain metastasis was one of the factors leading to the poor long-term prognosis of patients with lung adenocarcinoma (LUAD). The expression levels of immune genes in LUAD and LUAD brain metastases tissues were analyzed in GSE161116 dataset using the GEO2R, and the levels of differential immune genes in normal lung and LUAD tissues were verified. The biological functions and signaling mechanisms of the differential immune genes were explored via Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis. Cox regression analysis was used to screen the prognostic factors of LUAD patients, and a risk model was constructed. The role of the model was checked in the development of LUAD via receiver operating characteristic analysis, gene set enrichment analysis, and Cox regression analysis. Differentially expressed genes (DEGs) in brain metastasis were involved in the adaptive immune response, B cell differentiation, leukocyte migration, NF-kB signaling pathway, among others. The expression levels of TNFRSF11A, MS4A2, IL11, CAMP, MS4A1, and F2RL1 were independent factors affecting the poor prognosis of LUAD patients via Cox regression analysis and Akaike information criterion. In the constructed risk model, the overall survival of LUAD patients in the high-risk group was poor. The risk model was significantly related to the gender, clinical stage, T stage, lymph node metastasis, and survival status of LUAD patients. In addition, the risk model score was an independent risk factor that affected the poor prognosis of LUAD patients. TNFRSF11A, CAMP, F2RL1, IL11, MS4A1, and MS4A2 of the risk factors had diagnostic significance in LUAD brain metastasis and LUAD. The risk model participated in cytokinetic process, cell cycle, citrate cycle TCA cycle, etc. The risk model score was correlated with the levels of B cells memory, mast cells resting, macrophages M0, mast cells activated, neutrophils, eosinophils, T cells gamma delta, and immune cell markers. The risk model based on the LUAD brain metastasis immune factors TNFRSF11A, MS4A2, IL11, CAMP, MS4A1, and F2RL1 was related to the diagnosis, poor prognosis, and immune infiltrating cells of LUAD patients, and is expected to provide a reference for the development of treatment strategies for LUAD patients.