Identification of key factors shaping integrated levels of ACE2 and TMPRSS2 expression in head and neck squamous cell carcinoma.
Front Biosci (Landmark Ed)
; 26(10): 740-751, 2021 10 30.
Article
in English
| MEDLINE | ID: covidwho-1498507
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.Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Serine Endopeptidases
/
Carcinoma, Squamous Cell
/
Angiotensin-Converting Enzyme 2
/
COVID-19
/
Head and Neck Neoplasms
Type of study:
Prognostic study
Limits:
Humans
Language:
English
Journal:
Front Biosci (Landmark Ed)
Year:
2021
Document Type:
Article
Affiliation country:
4984
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