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用于预测肺腺癌淋巴结转移和预后的免疫相关基因特征的鉴定与验证

Identification and Validation of Immune-Related Gene Signature for Predicting Lymph Node Metastasis and Prognosis in Lung Adenocarcinoma.

作者信息

Jia Ran, Sui Zhilin, Zhang Hongdian, Yu Zhentao

机构信息

Department of Esophageal Cancer, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin's Clinical Research Center for Cancer, National Clinical Research Center of Cancer, Tianjin, China.

Department of Thoracic Surgery, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and PeKing Union Medical College, Shenzhen, China.

出版信息

Front Mol Biosci. 2021 May 24;8:679031. doi: 10.3389/fmolb.2021.679031. eCollection 2021.

DOI:10.3389/fmolb.2021.679031
PMID:34109216
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8182055/
Abstract

Lung cancer is a serious malignancy, and lung adenocarcinoma (LUAD) is the most common pathological subtype. Immune-related factors play an important role in lymph node metastasis. In this study, we obtained gene expression profile data for LUAD and normal tissues from the TCGA database and analyzed their immune-related genes (IRGs), and observed that 459 IRGs were differentially expressed. Further analysis of the correlation between differentially expressed IRGs and lymph node metastasis revealed 18 lymph node metastasis-associated IRGs. In addition, we analyzed the mutations status, function and pathway enrichment of these IRGs, and regulatory networks established through TF genes. We then identified eight IRGs (IKBKB, LTBR, MIF, PPARD, PPIA, PSME3, S100A6, SEMA4B) as the best predictors by LASSO Logistic analysis and used these IRGs to construct a model to predict lymph node metastasis in patients with LUAD (AUC 0.75; 95% CI: 0.7064-0.7978), and survival analysis showed that the risk score independently affected patient survival. We validated the predictive effect of risk scores on lymph node metastasis and survival using the GEO database as a validation cohort and the results showed good agreement. In addition, the risk score was highly correlated with infiltration of immune cells (mast cells activated, macrophages M2, macrophages M0 and B cells naïve), immune and stromal scores, and immune checkpoint genes (LTBR, CD40LG, EDA2R, and TNFRSF19). We identified key IRGs associated with lymph node metastasis in LUAD and constructed a reliable risk score model, which may provide valuable biomarkers for LUAD patients and further reveal the mechanism of its occurrence.

摘要

肺癌是一种严重的恶性肿瘤，肺腺癌（LUAD）是最常见的病理亚型。免疫相关因素在淋巴结转移中起重要作用。在本研究中，我们从TCGA数据库获得了LUAD和正常组织的基因表达谱数据，分析了它们的免疫相关基因（IRGs），观察到459个IRGs差异表达。对差异表达的IRGs与淋巴结转移之间的相关性进行进一步分析，发现了18个与淋巴结转移相关的IRGs。此外，我们分析了这些IRGs的突变状态、功能和通路富集情况，并通过转录因子（TF）基因建立了调控网络。然后，通过LASSO逻辑回归分析，我们确定了8个IRGs（IKBKB、LTBR、MIF、PPARD、PPIA、PSME3、S100A6、SEMA4B）作为最佳预测因子，并使用这些IRGs构建了一个模型来预测LUAD患者的淋巴结转移（AUC为0.75；95%CI：0.7064 - 0.7978），生存分析表明风险评分独立影响患者生存。我们使用GEO数据库作为验证队列，验证了风险评分对淋巴结转移和生存的预测效果，结果显示一致性良好。此外，风险评分与免疫细胞（活化肥大细胞、M2巨噬细胞、M0巨噬细胞和幼稚B细胞）浸润、免疫和基质评分以及免疫检查点基因（LTBR、CD40LG、EDA2R和TNFRSF19）高度相关。我们确定了与LUAD淋巴结转移相关的关键IRGs，并构建了一个可靠的风险评分模型，这可能为LUAD患者提供有价值的生物标志物，并进一步揭示其发生机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4db0/8182055/2e4d6f32fbc5/fmolb-08-679031-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4db0/8182055/9d3a80011112/fmolb-08-679031-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4db0/8182055/609f60464e55/fmolb-08-679031-g002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4db0/8182055/86223caad46c/fmolb-08-679031-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4db0/8182055/86f5fb4869fe/fmolb-08-679031-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4db0/8182055/26923aba4291/fmolb-08-679031-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4db0/8182055/00191bcd460d/fmolb-08-679031-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4db0/8182055/2e4d6f32fbc5/fmolb-08-679031-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4db0/8182055/9d3a80011112/fmolb-08-679031-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4db0/8182055/609f60464e55/fmolb-08-679031-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4db0/8182055/36948d012821/fmolb-08-679031-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4db0/8182055/6c88eb4b8e75/fmolb-08-679031-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4db0/8182055/86223caad46c/fmolb-08-679031-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4db0/8182055/86f5fb4869fe/fmolb-08-679031-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4db0/8182055/26923aba4291/fmolb-08-679031-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4db0/8182055/00191bcd460d/fmolb-08-679031-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4db0/8182055/2e4d6f32fbc5/fmolb-08-679031-g009.jpg

相似文献

[1]
Identification and Validation of Immune-Related Gene Signature for Predicting Lymph Node Metastasis and Prognosis in Lung Adenocarcinoma.

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[3]
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[4]
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[5]
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[6]
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An original aneuploidy-related gene model for predicting lung adenocarcinoma survival and guiding therapy.

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[8]
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[9]
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[10]
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本文引用的文献

[1]
Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries.

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Immunogenomic Gene Signature of Cell-Death Associated Genes with Prognostic Implications in Lung Cancer.

Cancers (Basel). 2021-1-5

[3]
Immune-Stromal Score Signature: Novel Prognostic Tool of the Tumor Microenvironment in Lung Adenocarcinoma.

Front Oncol. 2020-9-23

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The novel circ_0028171/miR-218-5p/IKBKB axis promotes osteosarcoma cancer progression.

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Pharmgenomics Pers Med. 2020-8-19

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Pan-Cancer Analysis of Immune Cell Infiltration Identifies a Prognostic Immune-Cell Characteristic Score (ICCS) in Lung Adenocarcinoma.

Front Immunol. 2020

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