Expression profile of SARS-CoV-2 cellular entry proteins in normal oral mucosa and oral squamous cell carcinoma
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Published on: September 22, 2023
Dipak Sapkota1, Sunita Sharma1, Tine M Søland1,2
1Department of Oral Biology, Faculty of Dentistry, University of Oslo, Oslo, Norway.
Objective:
Besides angiotensin converting enzyme 2 (ACE2), an active involvement of proteases (FURIN and/or TMPRSS2) is important for cellular entry of SARS-CoV-2. Therefore, a simultaneous expression profiling of entry proteins in a tissue might provide a better risk assessment of SARS-CoV-2 infection as compared to individual proteins. In an attempt to understand the relative susceptibility of oral squamous cell carcinoma (OSCC) lesions as compared to the normal oral mucosa (NOM) for SARS-CoV-2 attachment/entry, this study examined the mRNA and protein expression profiles of ACE2, FURIN, and TMPRSS2 in the corresponding tissues using public transcriptomic and proteomics datasets.
Methods And Methods:
Public transcriptomic and proteomics datasets (the Cancer Genome Atlas (TCGA)/the Genotype-Tissue Expression (GTEx), the Human Protein Atlas (HPA), and two independent microarray datasets) were used to examine the expression profiles of ACE2, TMPRSS2 and FURIN in NOM and OSCC.
Results:
ACE2, TMPRSS2, and FURIN mRNAs were detected in NOM, however, at lower levels as compared to other body tissues. Except for moderate up-regulation of FURIN, expression levels of ACE2 and TMPRSS2 mRNA were unchanged/down-regulated in OSCC as compared to the NOM.
Conclusions:
These results indicate that NOM may serve as a possible site for SARS-CoV-2 attachment, however, to a lesser extent as compared to organs with higher expression levels of the SARS-CoV-2 entry proteins. However, the evidence is lacking to suggest that expression status of entry proteins predisposes OSCC lesions to additional risk for SARS-CoV-2 attachment/entry as compared to NOM.
Insights
Normal oral mucosa shows lower expression of SARS-CoV-2 entry proteins compared to oral cancer lesions. This suggests normal oral tissue may be less susceptible to viral attachment, with no increased risk for oral squamous cell carcinoma.
Area of Science:
- Virology
- Oncology
- Molecular Biology
Background:
- Cellular entry of SARS-CoV-2 relies on angiotensin converting enzyme 2 (ACE2) and proteases like FURIN and TMPRSS2.
- Simultaneous profiling of these entry proteins can enhance risk assessment for SARS-CoV-2 infection.
- Oral squamous cell carcinoma (OSCC) and normal oral mucosa (NOM) susceptibility to SARS-CoV-2 requires investigation.
Purpose of the Study:
- To compare the expression profiles of SARS-CoV-2 entry proteins (ACE2, FURIN, TMPRSS2) in OSCC versus NOM.
- To assess the relative susceptibility of OSCC lesions and NOM to SARS-CoV-2 attachment and entry.
Main Methods:
- Utilized public transcriptomic and proteomics datasets, including TCGA, GTEx, and HPA.
- Examined mRNA and protein expression levels of ACE2, FURIN, and TMPRSS2 in NOM and OSCC tissues.
Main Results:
- ACE2, TMPRSS2, and FURIN mRNAs were detected in NOM, but at lower levels than in other body tissues.
- OSCC tissues showed unchanged or down-regulated ACE2 and TMPRSS2 mRNA expression compared to NOM.
- FURIN mRNA expression was moderately up-regulated in OSCC relative to NOM.
Conclusions:
- NOM may be a potential site for SARS-CoV-2 attachment, albeit less so than organs with higher entry protein expression.
- Current evidence does not support that the expression status of these entry proteins increases the risk for OSCC lesions regarding SARS-CoV-2 attachment/entry compared to NOM.

