A prognostic nomogram for lung adenocarcinoma based on immune-infiltrating Treg-related genes: from bench to bedside.
A prognostic nomogram for lung adenocarcinoma based on immune-infiltrating Treg-related genes: from bench to bedside.
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DOI：
10.21037/tlcr-20-822
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发表时间：
2021-01
影响因子：
4
通讯作者：
Zhang Z
中科院分区：
文献类型：
--
作者：
Wang X;Xiao Z;Gong J;Liu Z;Zhang M;Zhang Z
越来越多的证据表明，肿瘤微环境中淋巴细胞的浸润与肿瘤的发生和发展呈正相关，而Tregs（调节性T细胞）的作用一直存在争议。因此，我们试图发现Tregs在肺腺癌（LUAD）中的可能价值。LUAD的基因测序数据来自三个GEO （Gene Expression Omnibus）数据集gse10072、GSE32863和GSE43458；从CIBERSORTx门静脉中提取肿瘤浸润免疫细胞的相应组分。通过加权基因共表达网络分析（WGCNA）和蛋白相互作用网络分析（PPI）鉴定Tregs相关的重要模块和候选基因。候选基因在LUAD中的作用使用癌症基因组图谱（TCGA）数据库进一步验证。最后，我们通过绘制Kaplan-Meier （K-M）、受试者工作特征（ROC）和校准曲线，构建了预测LUAD预后的nomogram模型，说明了nomogram的性能。共纳入GEO数据库333个样本（196个肿瘤样本和137个正常样本）的10047个基因。通过WGCNA和PPI分析，我们确定了一个显著的黑色模块和36个与Treg相关的候选基因。接下来，利用TCGA数据进行Cox回归分析，对候选基因进行验证，筛选13个将LUAD患者划分为低危组或高危组的枢纽基因。低危患者的总生存期（OS）明显高于高危患者（3年OS: 70.2% vs. 35.2%； 5年OS: 36.6% vs. 0； P=1.651E-09）， ROC曲线下面积（AUC）较好（3年AUC: 0.733； 5年AUC: 0.777）。接下来，我们构建了一个结合枢纽基因和临床参数的生存图；与高危患者相比，低危患者预后仍较好（P=7.073E-13），且AUC更好（3年AUC: 0.763； 5年AUC: 0.873）。我们揭示了免疫浸润treg相关基因在LUAD中的作用，并构建了预后图，这可能有助于临床医生做出最佳治疗决策，帮助患者获得更好的结果。
Accumulating evidence suggests that lymphocyte infiltration in the tumor microenvironment is positively correlated with tumorigenesis and development, while the role of Tregs (regulatory T cells) has been controversial. Therefore, we attempted to discover the possible value of Tregs for lung adenocarcinoma (LUAD). The gene-sequencing data of LUAD were applied from three Gene Expression Omnibus (GEO) datasets—GSE10072, GSE32863 and GSE43458; the corresponding fractions of tumor-infiltrating immune cells were extracted from the CIBERSORTx portal. Weighted gene coexpression network analysis (WGCNA) and protein-protein interaction (PPI) network analysis were conducted to identify the significant module and candidate genes related to Tregs. The role of candidate genes in LUAD was further verified using data from The Cancer Genome Atlas (TCGA) database. Finally, we constructed a nomogram model to predict the prognosis of LUAD by plotting Kaplan-Meier (K-M), receiver operating characteristic (ROC) and calibration curves, which elucidated the performance of the nomogram. In total, 10,047 genes in 333 samples (196 tumor and 137 normal samples) from the GEO database were included. By WGCNA and PPI analysis, we identified a significant black module and 36 candidate genes related to Treg. Next, the candidate genes were verified using TCGA data by Cox regression analysis to screen 13 hub genes that stratified LUAD patients into low- or high-risk groups. Low-risk patients showed a significantly longer overall survival (OS) than high-risk patients (3-year OS: 70.2% vs. 35.2%; 5-year OS: 36.6% vs. 0; P=1.651E-09), and the areas under the ROC curves (AUCs) showed good (3-year AUC: 0.733; 5-year AUC: 0.777). Next, we constructed a survival nomogram combining the hub genes and clinical parameters; the low-risk patients still showed a favorable prognosis compared with that of the high-risk patients (P=7.073E-13), and the AUCs were better (3-year AUC: 0.763; 5-year AUC: 0.873). We revealed the role of immune-infiltrating Treg-related genes in LUAD and constructed a prognostic nomogram, which may help clinicians make optimal therapeutic decisions and help patients obtain better outcomes.
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影响因子：
3
作者：
Langfelder P;Horvath S
通讯作者：
Horvath S
影响因子：
14.5
作者：
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DOI：
10.4049/jimmunol.1301317
发表时间：
2013-08-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
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通讯作者：
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影响因子：
4.7
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影响因子：
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作者：
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Cai X