Characterization of Tumor Microenvironment and Prognosis of Regulatory T cells-Related Subtypes.

IF 3.5 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Xinwei Li, Meiyun Nie, Keke Yang, Xiaodong Qi, Xiong Wan, Ling Yang
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引用次数: 0

Abstract

Introduction: Regulatory T cells (Tregs) play an important role in the tumor microenvironment (TME). Currently, there have been no studies of Treg-related genes (TRGs) in lung adenocarcinoma (LUAD).

Methods: We integrated the Cancer Genome Atlas (TCGA) dataset with the Gene Expression Omnibus (GEO) dataset and divided the TCGA-GEO dataset patient samples into different cohorts by unsupervised clustering analysis based on the expression of TRGs in LUAD. By analyzing the TME characteristics of different cohorts, we assessed immune cell infiltration and function. In addition, we constructed Cox risk proportional regression models based on TRGs to predict patient prognosis.

Results: The results of unsupervised cluster analysis classified the TCGA-GEO dataset as "immune desert", "immune evasion" and "immune inflammation". Moreover, there was a significant survival differential among the three cohorts (p-value < 0.05). Based on the expression of 61 TRGs in LUAD, we screened TFRC, CTLA4, IL1R2, NPTN NPTN and METTL7A to construct a Cox risk proportional regression model to divide the TCGA-GEO dataset into a training cohort and a test cohort. Survival was significantly worse in the high-risk group than in the low-risk group in both the training and test cohorts (p-value < 0.05). Finally, the nomogram scoring system constructed by integrating the model risk scores with clinical parameters can well predict the 1, 3 and 5 year survival of patients.

Conclusion: In conclusion, based on our analysis of the TRGs of LUAD patients, we can classify the patient TME into different immune statuses, which provides insights into adopting appropriate treatment regimens for different patients.

.

调节性T细胞相关亚型肿瘤微环境特征及预后
导言:调节性T细胞(Regulatory T cells, Tregs)在肿瘤微环境(tumor microenvironment, TME)中起着重要作用。目前还没有treg相关基因(TRGs)在肺腺癌(LUAD)中的研究。方法:将癌症基因组图谱(Cancer Genome Atlas, TCGA)数据集与基因表达图谱(Gene Expression Omnibus, GEO)数据集进行整合,基于TRGs在LUAD中的表达,采用无监督聚类分析方法将TCGA-GEO数据集患者样本划分为不同的队列。通过分析不同队列的TME特征,评估免疫细胞浸润和功能。此外,我们构建了基于TRGs的Cox风险比例回归模型来预测患者预后。结果:无监督聚类分析结果将TCGA-GEO数据集分类为“免疫沙漠”、“免疫逃避”和“免疫炎症”。此外,三个队列之间存在显著的生存差异(p值< 0.05)。基于61个TRGs在LUAD中的表达,我们筛选TFRC、CTLA4、IL1R2、NPTN、NPTN和METTL7A,构建Cox风险比例回归模型,将TCGA-GEO数据集分为训练队列和测试队列。在训练组和测试组中,高危组的生存率明显低于低危组(p值< 0.05)。最后,将模型风险评分与临床参数相结合构建的nomogram评分系统能够较好地预测患者的1年、3年和5年生存期。结论:综上所述,通过对LUAD患者TRGs的分析,我们可以将患者TME划分为不同的免疫状态,为不同患者采取合适的治疗方案提供参考。
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来源期刊
Current medicinal chemistry
Current medicinal chemistry 医学-生化与分子生物学
CiteScore
8.60
自引率
2.40%
发文量
468
审稿时长
3 months
期刊介绍: Aims & Scope Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews and guest edited thematic issues written by leaders in the field covering a range of the current topics in medicinal chemistry. The journal also publishes reviews on recent patents. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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