In silico analysis of the key molecules of SARS-CoV-2: ACE2 and TMPRSS2 in head and neck cancer

Abstract

It has been reported that cancer patients are more susceptible to SARS-CoV-2 infection due to their immunocompromised state. Although ACE2 and TMPRSS2 are essential for SARS-CoV-2 virus entry, the significant role of these molecules in HNSC is still unknown. Thus, the study aimed to delineate the fundamental role these molecules in HNSC using a systems biology approach. The transcriptional profile of ACE2 and TMPRSS2 in HNSC was evaluated using the TIMER and UALCAN databases. The association between the mRNA levels of ACE2 and TMPRSS2 was assessed using GEPIA2. cBioPortal was used to assess the genetic alterations in the ACE2 and TMPRSS2 protein sequences involved in HNSC. The gene associated with COVID-19 and HNSC was identified using the CTD database. Finally, the STRING and PANTHER online platforms were used to construct a protein-protein interaction (PPI) network and to determine the functional role of genes retrieved from the CTD database, respectively. ACE2 expression was found to be unaltered in HNSC and uninfected HNSC datasets compared to normal and HPV-infected HNSC datasets, respectively. However, the TMPRSS2 levels in HNSC and HPV-infected HNSC were significantly (P ≤ 0.001) downregulated and upregulated compared to healthy controls and uninfected HNSC, respectively. A significant (P ≤ 0.014) but weak positive correlation was noted between ACE2 and TMPRSS2 in HNSC. The PPI network also showed significant involvement of COVID-19 and HNSC-related genes in catalysis, binding activity, and several cancers signaling pathways. Based on the in-silico analysis, it could be concluded that ACE2 and TMPRSS2, the key molecules of SARS-CoV-2, might be involved in HNSC. However, the long-term effects of SARS-CoV-2 infection, if any, on HNSC patients in clinical settings require further study.