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用于预测肺腺癌预后、免疫治疗疗效及肿瘤微环境的外泌体相关特征的鉴定

Identification of an Exosome-Related Signature for Predicting Prognosis, Immunotherapy Efficacy, and Tumor Microenvironment in Lung Adenocarcinoma.

作者信息

Lin Tao, Wang Hong, He Xi

机构信息

Department of Thoracic Surgery, Tangshan People's Hospital, Tangshan, China.

Tangshan Central Blood Station, Tangshan, China.

出版信息

J Oncol. 2022 Aug 3;2022:1827987. doi: 10.1155/2022/1827987. eCollection 2022.

Abstract

Accumulating evidence suggests that exosomes can affect lung adenocarcinoma (LUAD) progression. However, there is still a lack of understanding of the global influence of exosome-related genes (ERGs) on prognostic relevance, tumor microenvironment features, and immunotherapy responsiveness in patients with LUAD. In the TCGA dataset, differential analysis of 490 LUAD samples and 59 normal samples yielded 30 ERGs with differential expression. We have created a predictive signature based on 10 overall survival (OS)-related ERGs and confirmed it in two external cohorts (GSE72094 and GSE68465) via the least absolute shrinkage and selection operator (LASSO) and Cox regression analysis in the TCGA dataset. The new signature revealed superior robustness and prognostic capacity for overall patient survival. Univariate and multivariate Cox regression analyses indicated that this signature was an independent risk factor for survival in patients with LUAD. In addition, for predicting the 1-year, 3-year, and 5-year OS of LUAD patients, we developed a nomogram and confirmed its predictive ability via the C-index and calibration curve. In addition, patients categorized by risk score exhibited distinct immunological states, stemness index, immune subtypes, and immunotherapy response. In conclusion, we created a risk signature for LUAD that was tightly associated with the immune landscape and therapeutic response. Also, such a risk signature effectively promotes the ability of the clinicians in making more precise and individualized treatment recommendations for patients with LUAD.

摘要

越来越多的证据表明,外泌体可影响肺腺癌(LUAD)的进展。然而,对于外泌体相关基因(ERGs)对LUAD患者预后相关性、肿瘤微环境特征和免疫治疗反应性的整体影响仍缺乏了解。在TCGA数据集中,对490例LUAD样本和59例正常样本进行差异分析,得到30个差异表达的ERGs。我们基于10个与总生存期(OS)相关的ERGs创建了一个预测特征,并通过最小绝对收缩和选择算子(LASSO)以及TCGA数据集中的Cox回归分析在两个外部队列(GSE72094和GSE68465)中进行了验证。新的特征显示出对患者总体生存具有更高的稳健性和预后能力。单因素和多因素Cox回归分析表明,该特征是LUAD患者生存的独立危险因素。此外,为了预测LUAD患者的1年、3年和5年OS,我们绘制了列线图,并通过C指数和校准曲线证实了其预测能力。此外,根据风险评分分类的患者表现出不同的免疫状态、干性指数、免疫亚型和免疫治疗反应。总之,我们创建了一个与免疫格局和治疗反应密切相关的LUAD风险特征。此外,这种风险特征有效地提高了临床医生为LUAD患者做出更精确和个性化治疗建议的能力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da86/9365589/db5809f3e1ee/JO2022-1827987.001.jpg

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