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Low expression of TMPRSS2-a SARS-CoV-2 internalization protease-associates with basal subtype of head and neck
Jayesh Tiwari1, Nancy Tripathi1, Ravi Shanker Srivastava2
1Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology, Banaras Hindu University, Varanasi, India.
Abstract:
SARS-CoV-2 is a single-stranded RNA virus that has caused the ongoing COVID-19 pandemic. ACE2 and other genes utilized by SARS-CoV-2 to enter human cells have been shown to express in Head and Neck Squamous Cell Carcinoma (HNSCC) patients. However, their expression pattern in different subtypes has not been investigated. Hence, in the current study, we have analyzed the expression of ACE2, TMPRSS2 and FURIN in 649 HNSCC patients from two independent cohorts. Our analysis showed significantly lower expression of TMPRSS2 while significantly increased expression of ACE2 and FURIN in HPV-negative HNSCC. Comparison of expression of these genes in the three subtypes of HNSCC patients (basal, classical and inflamed/mesenchymal) showed no significant difference in the expression of ACE2 among the three subtypes; however, the basal subtype showed significantly reduced expression of TMPRSS2 but significantly increased expression of FURIN. Comparison of expression of these genes between the HPV-negative patients of basal subtype vs all others confirmed significantly lower expression of TMPRSS2 in HPV-negative patients of basal subtype as compared to all others. Our study shows that the different subtypes of HNSCC patients have different expression patterns of genes utilized by the SARS-CoV-2 to enter human cells, and hence, their susceptibility to SARS-CoV-2 may also be different. As the expression of TMPRSS2 is significantly lower in the HNSCC patients of the basal subtype, we predict that these patients would be less susceptible to SARS-CoV-2 infection than the patients of other subtypes. However, these findings need to be further validated.
Insights
Head and Neck Squamous Cell Carcinoma (HNSCC) patients show varied expression of SARS-CoV-2 entry genes. HPV-negative basal subtype HNSCC patients may have lower susceptibility to SARS-CoV-2 infection due to reduced TMPRSS2 expression.
Area of Science:
- Oncology
- Virology
- Genetics
Background:
- SARS-CoV-2, the virus causing COVID-19, utilizes host cell genes like ACE2, TMPRSS2, and FURIN for entry.
- These viral entry genes have been detected in Head and Neck Squamous Cell Carcinoma (HNSCC) patients.
- Expression patterns of these genes across different HNSCC subtypes remain largely uninvestigated.
Purpose of the Study:
- To analyze the expression of ACE2, TMPRSS2, and FURIN in HNSCC patient cohorts.
- To investigate differential gene expression patterns among HNSCC subtypes.
- To assess potential variations in SARS-CoV-2 susceptibility based on HNSCC subtype and HPV status.
Main Methods:
- Analysis of ACE2, TMPRSS2, and FURIN gene expression in 649 HNSCC patients from two independent cohorts.
- Comparison of gene expression between HPV-positive and HPV-negative HNSCC.
- Subtyping analysis based on basal, classical, and inflamed/mesenchymal phenotypes.
Main Results:
- Significantly lower TMPRSS2 expression and significantly higher ACE2 and FURIN expression were observed in HPV-negative HNSCC.
- No significant difference in ACE2 expression was found across HNSCC subtypes.
- The basal subtype exhibited significantly reduced TMPRSS2 and increased FURIN expression compared to other subtypes.
Conclusions:
- HNSCC subtypes display distinct expression profiles of SARS-CoV-2 entry genes.
- HPV-negative basal subtype HNSCC patients may exhibit reduced susceptibility to SARS-CoV-2 infection.
- Further validation is required to confirm the clinical implications of these findings.
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