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揭示食管癌中树突状细胞功能障碍的关键基因和分子机制:对新型诊断和治疗策略的启示

Uncovering key genes and molecular mechanisms of dendritic cell dysfunction in Esophageal Cancer: implications for Novel Diagnostic and therapeutic strategies.

作者信息

Li Yanqiang, Zeng Jing, Yu Chaoqun, Shen Weiyu, Xi Yong

机构信息

Department of Thoracic Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo University, Ningbo, 315040, Zhejiang, China.

Department of Thoracic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, China.

出版信息

Discov Oncol. 2024 Dec 18;15(1):790. doi: 10.1007/s12672-024-01620-x.

DOI:10.1007/s12672-024-01620-x
PMID:39692816
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11655908/
Abstract

Dendritic cells play a crucial role in initiating and regulating immune responses, and their dysfunction is strongly associated with esophageal cancer. In this study, we aimed to develop a predictive signature and identify key genes linked to dendritic cell dysfunction in esophageal cancer. Through bioinformatics analysis of gene expression data from the TCGA database, we identified a set of 603 genes significantly associated with dendritic cell function. Further analysis using Cox regression and LASSO regression revealed six genes (GDF15, GPT, KRTAP5-5, MMP12, SLC5A1, and C5orf52) that were strongly correlated with overall survival. The prognostic signature constructed from these genes demonstrated that patients in the high-risk group had poorer survival outcomes compared to those in the low-risk group. Immune infiltration analysis indicated a higher abundance of macrophages in the high-risk group, and correlation studies showed a strong positive association between the risk score and the expression of immune checkpoint markers PD1 and PD-L1. Drug sensitivity analysis suggested that Metformin, Gefitinib, and Lapatinib may be more effective in the low-risk group, while Pyrimethamine, Axitinib, and Rapamycin may be more beneficial for high-risk patients. In summary, we identified a 6-gene signature related to dendritic cell dysfunction that can predict prognosis in esophageal cancer, offering valuable insights for personalized therapeutic strategies.

摘要

树突状细胞在启动和调节免疫反应中起关键作用,其功能障碍与食管癌密切相关。在本研究中,我们旨在开发一种预测特征并鉴定与食管癌中树突状细胞功能障碍相关的关键基因。通过对TCGA数据库中基因表达数据的生物信息学分析,我们鉴定出一组603个与树突状细胞功能显著相关的基因。使用Cox回归和LASSO回归的进一步分析揭示了六个与总生存期密切相关的基因(GDF15、GPT、KRTAP5-5、MMP12、SLC5A1和C5orf52)。由这些基因构建的预后特征表明,高风险组患者的生存结果比低风险组患者更差。免疫浸润分析表明高风险组中巨噬细胞丰度更高,相关性研究表明风险评分与免疫检查点标志物PD1和PD-L1的表达之间存在强正相关。药物敏感性分析表明,二甲双胍、吉非替尼和拉帕替尼在低风险组中可能更有效,而乙胺嘧啶、阿昔替尼和雷帕霉素可能对高风险患者更有益。总之,我们鉴定出一个与树突状细胞功能障碍相关的6基因特征,可预测食管癌的预后,并为个性化治疗策略提供有价值的见解。

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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c027/11655908/db55189291d3/12672_2024_1620_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c027/11655908/6079d2a41ba7/12672_2024_1620_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c027/11655908/4ef9025b982a/12672_2024_1620_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c027/11655908/5d7a23048a2b/12672_2024_1620_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c027/11655908/b9e438617268/12672_2024_1620_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c027/11655908/40f578a466e2/12672_2024_1620_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c027/11655908/f9e48260b8b2/12672_2024_1620_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c027/11655908/5b3f5c8936db/12672_2024_1620_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c027/11655908/140023f64acd/12672_2024_1620_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c027/11655908/db55189291d3/12672_2024_1620_Fig9_HTML.jpg

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本文引用的文献

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A Bayesian Network Approach to Lung Cancer Screening: Assessing the Impact of Data Quantity, Quality, and the Combination of Data from Danish Electronic Health Records.一种用于肺癌筛查的贝叶斯网络方法:评估数据量、质量以及丹麦电子健康记录数据组合的影响。
Cancers (Basel). 2024 Nov 28;16(23):3989. doi: 10.3390/cancers16233989.
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NY-ESO-1 antigen: A promising frontier in cancer immunotherapy.NY-ESO-1 抗原:癌症免疫治疗的一个有前途的前沿领域。
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Tumor-derived DEFB1 induces immune tolerance by inhibiting maturation of dendritic cell and impairing CD8+ T cell function in esophageal squamous cell carcinoma.
肿瘤来源的DEFB1通过抑制树突状细胞成熟和损害食管鳞状细胞癌中CD8 + T细胞功能来诱导免疫耐受。
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The Multifaceted Functionality of Plasmacytoid Dendritic Cells in Gastrointestinal Cancers: A Potential Therapeutic Target?浆细胞样树突状细胞在胃肠道癌症中的多方面功能:一个潜在的治疗靶点?
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Advances in diagnosis and management of cancer of the esophagus.食管癌的诊断与治疗进展。
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