Genetic Susceptibility of ACE2 and TMPRSS2 in Six Common Cancers and Possible Impacts on COVID-19

Abstract

Purpose Coronavirus disease 2019 (COVID-19) pandemic has spread worldwide rapidly and patients with cancer have been considered as a vulnerable group for this infection. This study aimed to examine the expressions of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) in tumor tissues of six common cancer types.Materials and Methods The expression levels of ACE2 and TMPRSS2 in tumors and control samples were obtained from online databases. Survival prognosis and biological functions of these genes were investigated for each tumor type.Results There was the overexpression of ACE2 in colon and stomach adenocarcinomas compared to controls, meanwhile colon and prostate adenocarcinomas showed a significantly higher expression of TMPRSS2. Additionally, survival prognosis analysis has demonstrated that upregulation of ACE2 in liver hepatocellular carcinoma was associated with higher overall survival (hazard ratio, 0.65; p=0.016) and disease-free survival (hazard ratio, 0.66; p=0.007), while overexpression of TMPRSS2 was associated with a 26% reduced risk of death in lung adenocarcinoma (p=0.047) but 50% increased risk of death in breast invasive carcinoma (p=0.015).Conclusion There is a need to take extra precautions for COVID-19 in patients with colorectal cancer, stomach cancer, and lung cancer. Further information on other types of cancer at different stages should be investigated.

Neuropilin-1: A feasible link between liver pathologies and COVID-19

“…Interestingly, cancer survivors had more likely to suffer disease complications than healthy people but less likely than cancer patients[ 98 ]. Recent studies describe a possible link between SARS-CoV-2 receptor ACE2 in cancer tissues and increased risk of infection[ 99 ]. In liver cancer, Dai et al [ 100 ] found that upregulated expression of ACE2, the primary SARS-CoV-2 ligand in infected cells, was related to improved survival in HCC patients.…”

COVID-19 and Malignancy: Exploration of the possible genetic and epigenetic interlinks and overview of the vaccination scenario

“…Another similar study was conducted by Hoang et al [47] where they tried to assess the expression level of ACE2 and TMPRSS2 in 6 cancer types [Lung Adenocarcinoma (LUAD), Breast Invasive Carcinoma (BRCA), COAD, PRAD, STAD, and Liver Hepatocellular Carcinoma (LIHC)] and compared those values found in malignancies to that of non-cancer patients. With GEPIA2 [33] , they found that mRNA levels of ACE2 expression were significantly higher in COAD and STAD which is similar to the findings of Li et al [32] .…”

“…Another interesting fact is that they tried to narrow down the affected pathways. KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analysis for ACE2 and top 100 co-expressed genes showed that the most significant pathways were phenylalanine metabolism (p=0.003), tryptophan metabolism (p=0.001), vitamin digestion and absorption (p < 0.001), steroid hormone biosynthesis (p=0.003), fat digestion and absorption (p=0.001), and Renin-Angiotensin System (RAAS) (p=0.006) [47] . Such extensive involvement of metabolic pathways was also supported by a metabolism-linked hypothesis regarding NAMPT/ NAD and RAAS and this hypothesis seems to materialize a connection between cardiovascular function [48] , lung failure and [49] SARS infections [50] .…”

“…All these in-silico studies mainly estimate the expression levels of such genes which play pivotal roles in COVID-19 infection [ 32 , 35 , 47 ]. The reason of such differential expression of these genes in cancer and non-cancer populations plausibly can shed more light on the phenomenon of higher mortality and vulnerability rates observed in cancer patients suffering from COVID-19 compared to those of their non-cancer COVID-19 counterparts.…”

Bioinformatics approach to identify common gene signatures of patients with coronavirus 2019 and lung adenocarcinoma

“…Bioinformatics studies of COVID-19 and cancer focus on the expression in cancers of key factors such as angiotensin-converting enzyme 2 (ACE2), transmembrane serine protease 2 (TMPRSS2), and neuropilin-1 (Chai et al 2020 ; Ahmadi et al 2021 ; Hoang et al 2021 ; Hu et al 2021a ), although few studies report a common genetic signature of COVID-19 and cancer, particularly of patients with LUAD, as well as potential underlying biological processes. Understanding the common genetic features between these two diseases and the underlying biological processes can help to explore the pathophysiological processes in patients with both diseases, improve the medical management of these patients, and allow the search for appropriate treatment modalities and medclines.…”