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2019冠状病毒病调控因子相关基因组及预后特征的泛癌分析

Pan-Cancer Analysis of Genomic and Prognostic Characteristics Associated With Coronavirus Disease 2019 Regulators.

作者信息

Zhang Jian, Jiang Huali, Du Kunpeng, Xie Tao, Wang Baiyao, Chen Chengcong, Cen Bohong, Yuan Yawei, Ye Jiacai

机构信息

Department of Radiation Oncology, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Disease, Guangzhou, China.

Guangzhou Medical University, Guangzhou, China.

出版信息

Front Med (Lausanne). 2021 Aug 11;8:662460. doi: 10.3389/fmed.2021.662460. eCollection 2021.

Abstract

Cancer patients are alleged to have poor coronavirus disease 2019 (COVID-19) outcomes. However, no systematic or comprehensive analyses of the role and mechanisms of COVID-19 receptor-related regulators in cancer are available. We comprehensively evaluated the genomic alterations and their clinical relevance of six COVID-19 receptor-related regulators [transmembrane serine protease 2 (TMPRSS2), angiotensinogen (AGT), angiotensin-converting enzyme 1 (ACE1), solute carrier family 6 member 19 (SLC6A19), angiotensin-converting enzyme 2 (ACE2), and angiotensin II receptor type 2 (AGTR2)] across a broad spectrum of solid tumors. RNA-seq data, single nucleotide variation data, copy number variation data, methylation data, and miRNA-mRNA interaction network data from The Cancer Genome Atlas (TCGA) of 33 solid tumors were analyzed. We assessed the sensitivities of drugs targeting COVID-19 receptor-related regulators, using information from the Cancer Therapeutics Response Portal database. We found that there are widespread genetic alterations of COVID-19 regulators and that their expression levels were significantly correlated with the activity of cancer hallmark-related pathways. Moreover, COVID-19 receptor-related regulators may be used as prognostic biomarkers. By mining the genomics of drug sensitivities in cancer databases, we discovered a number of potential drugs that may target COVID-19 receptor-related regulators. This study revealed the genomic alterations and clinical characteristics of COVID-19 receptor-related regulators across 33 cancers, which may clarify the potential mechanism between COVID-19 receptor-related regulators and tumorigenesis and provide a novel approach for cancer treatments.

摘要

癌症患者被认为2019冠状病毒病(COVID-19)预后较差。然而,目前尚无关于COVID-19受体相关调节因子在癌症中的作用和机制的系统或全面分析。我们全面评估了六种COVID-19受体相关调节因子[跨膜丝氨酸蛋白酶2(TMPRSS2)、血管紧张素原(AGT)、血管紧张素转换酶1(ACE1)、溶质载体家族6成员19(SLC6A19)、血管紧张素转换酶2(ACE2)和血管紧张素II 2型受体(AGTR2)]在广泛实体瘤中的基因组改变及其临床相关性。分析了来自33种实体瘤的癌症基因组图谱(TCGA)的RNA测序数据、单核苷酸变异数据、拷贝数变异数据、甲基化数据和miRNA-mRNA相互作用网络数据。我们利用癌症治疗反应门户数据库的信息评估了靶向COVID-19受体相关调节因子的药物的敏感性。我们发现COVID-19调节因子存在广泛的基因改变,其表达水平与癌症特征相关通路的活性显著相关。此外,COVID-19受体相关调节因子可能用作预后生物标志物。通过挖掘癌症数据库中的药物敏感性基因组学,我们发现了一些可能靶向COVID-19受体相关调节因子的潜在药物。本研究揭示了33种癌症中COVID-19受体相关调节因子的基因组改变和临床特征,这可能阐明COVID-19受体相关调节因子与肿瘤发生之间的潜在机制,并为癌症治疗提供一种新方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9781/8385656/2545e2e75b7c/fmed-08-662460-g0001.jpg

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