通过生物信息学分析肺腺癌免疫细胞浸润的特征,预测免疫治疗的效果。
Analyzing the characteristics of immune cell infiltration in lung adenocarcinoma via bioinformatics to predict the effect of immunotherapy.
机构信息
State Key Laboratory of Biotherapy of China, Division of Pulmonary Diseases, Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, China.
出版信息
Immunogenetics. 2021 Oct;73(5):369-380. doi: 10.1007/s00251-021-01223-8. Epub 2021 Jul 24.
Recent studies have shown that tumor immune cell infiltration (ICI) is associated with immunotherapy sensitivity and the prognosis of lung adenocarcinoma (LUAD). However, the immunoinfiltrative landscape of LUAD has not been elucidated. We propose two computational algorithms to unravel the ICI landscape to evaluate the efficacy of immunotherapy in LUAD patients. The raw data of LUAD patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were analyzed. After merging these datasets and removing the batch differences, we used the Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) algorithm to obtain the immune cell content of all the samples. The unsupervised consistency clustering algorithm was used to analyze the ICI subtypes, and three subgroups were obtained. In addition, the unsupervised consistency clustering algorithm was used to analyze the differentially expressed genes (DEGs) of the ICI subtypes and obtain three ICI gene clusters. Finally, the ICI score was determined by using principal component analysis (PCA) for the gene signature. The ICI score of LUAD patients ranged from - 32.26 to 12.89 and represents the prognosis and the response to immunotherapy. High ICI scores were characterized by the T cell receptor signaling pathway, B cell receptor signaling pathway, and natural killer cell-mediated cytotoxicity, suggesting that some immune cells were activated and had increased activity, which may be the cause of the better prognosis for patients with high ICI scores. Additionally, patients with higher ICI scores showed a significant immune therapeutic advantage and clinical benefit. This study shows that the ICI score may be a potent prognostic biomarker and predictor of therapy with immune checkpoint inhibitors.
最近的研究表明,肿瘤免疫细胞浸润(ICI)与肺腺癌(LUAD)的免疫治疗敏感性和预后相关。然而,LUAD 的免疫浸润景观尚未阐明。我们提出了两种计算算法来揭示 ICI 景观,以评估免疫疗法在 LUAD 患者中的疗效。分析了来自癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)的 LUAD 患者的原始数据。在合并这些数据集并消除批次差异后,我们使用细胞类型鉴定通过估计 RNA 转录物的相对亚群(CIBERSORT)算法获得所有样本的免疫细胞含量。使用无监督一致性聚类算法分析 ICI 亚型,并获得三个亚组。此外,无监督一致性聚类算法用于分析 ICI 亚型的差异表达基因(DEG),并获得三个 ICI 基因簇。最后,通过主成分分析(PCA)确定基因特征的 ICI 得分。LUAD 患者的 ICI 得分范围为-32.26 至 12.89,代表预后和对免疫治疗的反应。高 ICI 得分的特征是 T 细胞受体信号通路、B 细胞受体信号通路和自然杀伤细胞介导的细胞毒性,表明一些免疫细胞被激活且活性增加,这可能是高 ICI 得分患者预后较好的原因。此外,ICI 评分较高的患者表现出显著的免疫治疗优势和临床获益。这项研究表明,ICI 评分可能是一种有效的预后生物标志物和免疫检查点抑制剂治疗的预测因子。