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基于生物信息学分析的子宫内膜癌中 PD-1 共表达基因分析及其调控网络。

PD-1 Coexpression Gene Analysis and the Regulatory Network in Endometrial Cancer Based on Bioinformatics Analysis.

机构信息

Third Central Hospital of Tianjin, Tianjin, China.

Tianjin Key Laboratory of Artificial Cell, China.

出版信息

Biomed Res Int. 2021 May 25;2021:9923434. doi: 10.1155/2021/9923434. eCollection 2021.

DOI:10.1155/2021/9923434
PMID:34124265
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8172290/
Abstract

Gynecological malignancies are tumors of the female reproductive system, mainly cervical cancer, endometrial cancer, and ovarian cancer. Endometrial cancer (EC) is the most common gynecological malignant tumor in developed countries. The aim of this study was to construct a network of programmed cell death protein 1 (PD-1) coexpressed genes through bioinformatics analysis and screen the potential biomarkers of PD-1 in endometrial cancer. In addition, genes and pathways involved in PD-1 and modulating tumor immune status were identified. We select the EC transcriptomic dataset in TCGA to retrieve gene sets on the cBioPortal platform, and the PD-1 coexpressed genes were obtained on the platform. GO and KEGG enrichment analysis of coexpressed genes was performed using the DAVID database. The target protein-protein interaction (PPI) network was constructed using Cytoscape 3.7.1 software, and the hub genes were then screened. A total of 976 coexpression genes were obtained. The enrichment analysis showed that PD-1 coexpressed genes were significantly enriched in overall components of the cell structure, the interaction of cytokines with cytokine receptors, chemokine signaling pathways, and cell adhesion molecules (CAMs). Ten hub genes were obtained by node degree analysis. CD3E gene is involved in the prognosis and immune process of EC, and the expression level is related to PD-1 (Pearson correlation coefficient is 0.82, < 0.01). Patients with low CD3E gene expression in EC have a poor prognosis. The coexpression hub genes of PD-1 are related to immunity, in which CD3E is a prognostic marker that is involved in the PD-1/PD-L1-induced tumor immune escape. This study provides a new area to study the mechanism of PD-1/PD-L1 in EC and the precise treatment with targeted drugs.

摘要

妇科恶性肿瘤是女性生殖系统的肿瘤,主要包括宫颈癌、子宫内膜癌和卵巢癌。子宫内膜癌(EC)是发达国家最常见的妇科恶性肿瘤。本研究旨在通过生物信息学分析构建程序性细胞死亡蛋白 1(PD-1)共表达基因网络,并筛选 PD-1 在子宫内膜癌中的潜在生物标志物。此外,还鉴定了与 PD-1 相关并调节肿瘤免疫状态的基因和途径。我们从 TCGA 中选择 EC 转录组数据集,在 cBioPortal 平台上检索基因集,并在该平台上获得 PD-1 共表达基因。使用 DAVID 数据库对共表达基因进行 GO 和 KEGG 富集分析。使用 Cytoscape 3.7.1 软件构建目标蛋白-蛋白相互作用(PPI)网络,然后筛选枢纽基因。共获得 976 个共表达基因。富集分析表明,PD-1 共表达基因在细胞结构的整体成分、细胞因子与细胞因子受体的相互作用、趋化因子信号通路和细胞黏附分子(CAM)中显著富集。通过节点度分析获得了 10 个枢纽基因。CD3E 基因参与 EC 的预后和免疫过程,其表达水平与 PD-1 相关(Pearson 相关系数为 0.82,<0.01)。EC 中 CD3E 基因低表达的患者预后不良。PD-1 共表达的枢纽基因与免疫有关,其中 CD3E 是一个预后标志物,参与 PD-1/PD-L1 诱导的肿瘤免疫逃逸。本研究为研究 PD-1/PD-L1 在 EC 中的作用机制以及靶向药物的精确治疗提供了一个新的领域。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c26/8172290/d8dff2b89ab1/BMRI2021-9923434.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c26/8172290/01b41998e608/BMRI2021-9923434.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c26/8172290/221ed49bb978/BMRI2021-9923434.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c26/8172290/5caf1f2b08fd/BMRI2021-9923434.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c26/8172290/d8dff2b89ab1/BMRI2021-9923434.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c26/8172290/01b41998e608/BMRI2021-9923434.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c26/8172290/221ed49bb978/BMRI2021-9923434.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c26/8172290/5caf1f2b08fd/BMRI2021-9923434.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c26/8172290/d8dff2b89ab1/BMRI2021-9923434.004.jpg

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Deep and Durable Response With Combination CTLA-4 and PD-1 Blockade in Mismatch Repair (MMR)-proficient Endometrial Cancer.CTLA-4 和 PD-1 联合阻断治疗在错配修复(MMR)功能正常的子宫内膜癌中具有深度和持久的应答。
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