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肺腺癌中免疫相关特征的建立与验证

Establishment and validation of an immune-associated signature in lung adenocarcinoma.

作者信息

Wang Zhenyu, Chen Xiaoman

机构信息

Department of Molecular Biology and Biochemistry, Basic Medical College of Nanchang University, Nanchang, PR China.

Department of Molecular Biology and Biochemistry, Basic Medical College of Nanchang University, Nanchang, PR China.

出版信息

Int Immunopharmacol. 2020 Nov;88:106867. doi: 10.1016/j.intimp.2020.106867. Epub 2020 Aug 13.

Abstract

Recent studies demonstrated that immune associated genes (IAGs) played an important role in the treatment of lung adenocarcinoma (LUAD). In the research, we established an IAGs signature and validated its prognostic value in LUAD by using bioinformatic methods and public databases. Based on the RNA-Seq samples from The Cancer Genome Atlas (TCGA), 576 differentially expressed IAGs were firstly identified. The R package coxph was used to select significant prognostic IAGs using both univariate and multivariate analyses. As a result, four IAGs (SCG2, CCL20, CAT, S100P) were finally screened in an IAGs signature. Based on these four IAGs, LASSO (least absolute shrinkage and selection operator) Cox regression analysis was used to construct a Risk score prognostic model and survival analysis revealed that high risk score was significantly associated with poor survival outcomes, which was validated in the external datasets GSE68465 and GSE31210. In addition, Risk score was found to be significantly associated with stage, lymphatic involvement, tumor metastasis and immune cells (B cells and dendritic cells) infiltration. Moreover, it was found that TP53 and EGFR had a higher mutation frequency in high risk group. Then a nomogram with clinical characteristics was established to superiorly predict prognosis of LUAD patients, and calibration plots and ROC analysis proved its accuracy. We believe that our findings can be conveniently used for individualized prediction of the clinical prognosis for LUAD patients, but further clinical trials and experimental exploration are needed to validate our observations.

摘要

近期研究表明,免疫相关基因(IAGs)在肺腺癌(LUAD)治疗中发挥重要作用。在本研究中,我们建立了一个IAGs特征,并通过生物信息学方法和公共数据库验证了其在LUAD中的预后价值。基于来自癌症基因组图谱(TCGA)的RNA测序样本,首先鉴定出576个差异表达的IAGs。使用R包coxph通过单变量和多变量分析来选择具有显著预后意义的IAGs。结果,最终在一个IAGs特征中筛选出四个IAGs(SCG2、CCL20、CAT、S100P)。基于这四个IAGs,使用最小绝对收缩和选择算子(LASSO)Cox回归分析构建风险评分预后模型,生存分析显示高风险评分与较差的生存结果显著相关,这在外部数据集GSE68465和GSE31210中得到验证。此外,发现风险评分与分期、淋巴受累、肿瘤转移和免疫细胞(B细胞和树突状细胞)浸润显著相关。而且,发现在高风险组中TP53和EGFR具有更高的突变频率。然后建立了一个包含临床特征的列线图以更好地预测LUAD患者的预后,校准图和ROC分析证明了其准确性。我们相信我们的发现可方便地用于LUAD患者临床预后的个体化预测,但需要进一步的临床试验和实验探索来验证我们的观察结果。

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