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构建用于预测生存的鳞状细胞肺癌预后免疫特征。

Construction of a Prognostic Immune Signature for Squamous-Cell Lung Cancer to Predict Survival.

机构信息

Integrative Cancer Centre, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.

Department of Oncology, Guangzhou Chest Hospital, Guangzhou, China.

出版信息

Front Immunol. 2020 Sep 15;11:1933. doi: 10.3389/fimmu.2020.01933. eCollection 2020.


DOI:10.3389/fimmu.2020.01933
PMID:33072067
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7533590/
Abstract

BACKGROUND: Limited treatment strategies are available for squamous-cell lung cancer (SQLC) patients. Few studies have addressed whether immune-related genes (IRGs) or the tumor immune microenvironment can predict the prognosis for SQLC patients. Our study aimed to construct a signature predict prognosis for SQLC patients based on IRGs. METHODS: We constructed and validated a signature from SQLC patients in The Cancer Genome Atlas (TCGA) using bioinformatics analysis. The underlying mechanisms of the signature were also explored with immune cells and mutation profiles. RESULTS: A total of 464 eligible SQLC patients from TCGA dataset were enrolled and were randomly divided into the training cohort ( = 232) and the testing cohort ( = 232). Eight differentially expressed IRGs were identified and applied to construct the immune signature in the training cohort. The signature showed a significant difference in overall survival (OS) between low-risk and high-risk cohorts ( < 0.001), with an area under the curve of 0.76. The predictive capability was verified with the testing and total cohorts. Multivariate analysis revealed that the 8-IRG signature served as an independent prognostic factor for OS in SQLC patients. Naive B cells, resting memory CD4 T cells, follicular helper T cells, and M2 macrophages were found to significantly associate with OS. There was no statistical difference in terms of tumor mutational burden between the high-risk and low-risk cohorts. CONCLUSION: Our study constructed and validated an 8-IRG signature prognostic model that predicts clinical outcomes for SQLC patients. However, this signature model needs further validation with a larger number of patients.

摘要

背景:目前针对鳞状细胞肺癌(SQLC)患者的治疗策略有限。很少有研究探讨免疫相关基因(IRGs)或肿瘤免疫微环境是否可以预测 SQLC 患者的预后。我们的研究旨在构建基于 IRGs 的预测 SQLC 患者预后的特征。

方法:我们使用生物信息学分析从癌症基因组图谱(TCGA)中的 SQLC 患者中构建和验证了一个特征。还通过免疫细胞和突变谱探索了该特征的潜在机制。

结果:共纳入 TCGA 数据集的 464 名符合条件的 SQLC 患者,并将其随机分为训练队列(n=232)和测试队列(n=232)。鉴定出 8 个差异表达的 IRGs,并应用于训练队列构建免疫特征。该特征在低风险和高风险队列之间的总生存期(OS)中显示出显著差异(<0.001),曲线下面积为 0.76。该预测能力在测试和总队列中得到了验证。多变量分析显示,8-IRG 特征是 SQLC 患者 OS 的独立预后因素。幼稚 B 细胞、静息记忆 CD4 T 细胞、滤泡辅助 T 细胞和 M2 巨噬细胞与 OS 显著相关。高风险和低风险队列之间的肿瘤突变负担没有统计学差异。

结论:我们构建并验证了一个 8-IRG 特征预后模型,可预测 SQLC 患者的临床结局。然而,该特征模型需要更多患者的进一步验证。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9b8/7533590/3678dad1b68e/fimmu-11-01933-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9b8/7533590/a9a2f6bc31c0/fimmu-11-01933-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9b8/7533590/ea37fec895e2/fimmu-11-01933-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9b8/7533590/70c39049fc16/fimmu-11-01933-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9b8/7533590/5bbf1614d7d1/fimmu-11-01933-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9b8/7533590/a3c0baaf8cb5/fimmu-11-01933-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9b8/7533590/3678dad1b68e/fimmu-11-01933-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9b8/7533590/a9a2f6bc31c0/fimmu-11-01933-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9b8/7533590/ea37fec895e2/fimmu-11-01933-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9b8/7533590/70c39049fc16/fimmu-11-01933-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9b8/7533590/5bbf1614d7d1/fimmu-11-01933-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9b8/7533590/a3c0baaf8cb5/fimmu-11-01933-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9b8/7533590/3678dad1b68e/fimmu-11-01933-g006.jpg

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Comprehensive Genomic Profiling Identifies Novel Genetic Predictors of Response to Anti-PD-(L)1 Therapies in Non-Small Cell Lung Cancer.

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