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

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

doi:10.3389/fmed.2021.662460

Abstract

Background: 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.Methods: 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.Results: 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.Conclusion: 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.

Highlights

The severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) virus has resulted in the ongoing coronavirus disease 2019 (COVID-19) pandemic
The number of samples for each cancer type ranged from 48 to 1,098, where only 14 cancer types that harbored over 10 pairs of tumor and normal samples were incorporated into analyses, namely, bladder urothelial carcinoma (BLCA), breast invasive carcinoma (BRCA), colon adenocarcinoma (COAD), esophageal carcinoma (ESCA), head and neck squamous cell carcinoma (HNSC), kidney chromophobe (KICH), kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC), prostate adenocarcinoma (PRAD), stomach adenocarcinoma (STAD), and thyroid carcinoma (THCA)
The results indicated that COVID-19 may be more infectious in BRCA, LUSC, KIRC, STAD, LUAD, HNSC, and BLCA patients than in the normal population

Summary

Introduction

The severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) virus has resulted in the ongoing coronavirus disease 2019 (COVID-19) pandemic. ACE2 degrades Ang II, counteracting its chronic effects, and serves as the SARS-CoV-2 receptor. The spike protein (S protein) of SARS-CoV binds to cell surface ACE2 receptors [9]. Transmembrane serine protease 2 (TMPRSS2), a member of the serine protease family, facilitates human coronavirus infections (SARS-CoV and SARS-CoV-2) via proteolytic cleavage of the ACE2 receptor, which promotes viral uptake and cleavage of coronavirus spike glycoproteins, activating glycoproteins for host cell entry [12,13,14]. Solute carrier family 6 member 19 (SLC6A19), a SARS-CoV-2 co-receptor, is a neutral amino acid transporter and forms a heterodimer with ACE2 [15]. No systematic or comprehensive analyses of the role and mechanisms of COVID-19 receptor-related regulators in cancer are available

Methods

Results

Discussion

Conclusion