Abstract
Objectives: To quantify the integrated levels of ACE2 and TMPRSS2, the two well-recognized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry-related genes, and to further identify key factors contributing to SARS-CoV-2 susceptibility in head and neck squamous cell carcinoma (HNSC). Methods: We developed a metric of the potential for tissue infected with SARS-CoV-2 ("TPSI") based on ACE2 and TMPRSS2 transcript levels and compared TPSI levels between tumor and matched normal tissues across 11 tumor types. For further analysis of HNSC, weighted gene co-expression network analysis (WGCNA), functional analysis, and single sample gene set enrichment analysis (ssGSEA) were conducted to investigate TPSI-relevant biological processes and their relationship with the immune landscape. TPSI-related factors were identified from clinical and mutational domains, followed by lasso regression to determine their relative effects on TPSI levels. Results: TPSI levels in tumors were generally lower than in the normal tissues. In HNSC, the genes highly associated with TPSI were enriched in viral entry-related processes, and TPSI levels were positively correlated with both eosinophils and T helper 17 (Th17) cell infiltration. Furthermore, the site of onset, human papillomaviruses (HPV) status, and nuclear receptor binding SET domain protein 1 (NSD1) mutations were identified as the most important factors shaping TPSI levels. Conclusions: This study identified the infection risk of SARS-CoV-2 between tumor and normal tissues, and provided evidence for the risk stratification of HNSC.
Highlights
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen causing Coronavirus disease 2019 (COVID-19) [1]
Considering the high prevalence of COVID-19 in cancer patients, we explored the distribution of Angiotensin-converting enzyme 2 (ACE2) and TMPRSS2 expression in 11 cancer types and their corresponding normal tissues
We found no evident relationships between the potential for SARS-CoV-2 infection (TPSI) levels with gender, age, and smoking; the TPSI levels were lower in oral squamous cell carcinoma (OSCC) and human papillomaviruses (HPV)-head and neck squamous cell carcinoma (HNSC)
Summary
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen causing Coronavirus disease 2019 (COVID-19) [1]. Angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) are two wellrecognized factors involved in SARS-CoV-2 cell entry [10,11,12]. SARS-CoV-2 infection begins with the binding of the viral spike (S) protein to the ACE2 receptor, allowing viral adhesion to the surface of host cells [10, 11]. This binding is followed by TMPRSS2-enabling S-protein priming [12]. Nafamostat mesilate can inhibit Middle East respiratory syndrome (MERS)-CoV S proteinmediated viral membrane fusion with TMPRSS2- expressing Calu-3 lung host cells by inhibiting TMPRSS2 protease activity [20]. Because the S proteins of MERS-Cov and SARS-CoV-2 share considerable amino acid sequence homology [21], nafamostat mesilate may inhibit SARSCoV-2 cell entry
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
