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

2021 ◽  
Vol 8 ◽  
Author(s):  
Jian Zhang ◽  
Huali Jiang ◽  
Kunpeng Du ◽  
Tao Xie ◽  
Baiyao Wang ◽  
...  

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.

2021 ◽  
Vol 46 (2) ◽  
pp. 245-249
Author(s):  
Monika Cahova ◽  
Martin Kveton ◽  
Vojtech Petr ◽  
David Funda ◽  
Helena Dankova ◽  
...  

<b><i>Background:</i></b> Preclinical studies suggested that pharmacological inhibition of the renin-angiotensin-aldosterone system (RAAS) by ACE inhibitors (ACEis) or angiotensin II receptor blockers (ARBs) may increase local angiotensin-converting enzyme 2 (<i>ACE2</i>) expression. <b><i>Methods:</i></b> In this study, we evaluated the effect of ACEi or ARB treatment on expression of <i>ACE2</i>, <i>ACE</i>, and <i>AGTR1</i> in 3-month protocol kidney allograft biopsies of stable patients using RT-qPCR (<i>n</i> = 48). Protein ACE2 expression was assessed using immunohistochemistry from paraffin sections. <b><i>Results:</i></b> The therapy with RAAS blockers was not associated with increased <i>ACE2, ACE</i>, or <i>ATGR1</i> expression in kidney allografts and also ACE2 protein immunohistochemistry did not reveal differences among groups. <b><i>Conclusions:</i></b> ACEis or ARBs in kidney transplant recipients do not affect local ACE2 expression. This observation supports long-term RAAS treatment in kidney transplant recipients, despite acute complications such as COVID-19 where ACE2 serves as the entry protein for infection.


Author(s):  
Azza S. Jabbar ◽  
Nadheera F. Neamah ◽  
Ahmed H. Al-Darraji

Abstract Objectives Hypertension is a very common cardiovascular disease. Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARBs) are widely used to treat hypertension. Many patients with hypertension are vulnerable to the antihypertensive adverse effects, which potentially reduces the adherence rate. Therefore, we conducted this study in order to evaluate the safety profile of both classes (ACEi and ARBs) on respiratory functions. Methods Two main groups of subjects were studied: first group is healthy control subjects and the second group is hypertensive patients, which was subdivided into subgroups in order to investigate the effect of all tested medications (captopril, enalapril, lisinopril, losartan, and valsartan). Respiratory efficiency was evaluated by measuring pulmonary function tests: FEV1, FVC, and FEV1%. Measurements were done using micromedical spirometer. Results We found that ARBs do not impair normal respiratory functions as measured by FEV1, FEV1%, and FVC in hypertensive patients. While ACEi treatments significantly reduced FEV1, FEV1%, and FVC compared to the other groups. Conclusions ARBs are not associated with any harmful effects on respiratory functions in hypertensive patients, unlike ACEi. As such, they could represent a first-choice treatment for hypertensive patients who are at high risk to the respiratory adverse effects.


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