IMR Press / FBL / Volume 26 / Issue 10 / DOI: 10.52586/4984
Open Access Article
Identification of key factors shaping integrated levels of ACE2 and TMPRSS2 expression in head and neck squamous cell carcinoma
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1 The VIP Department, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases, 110002 Shenyang, Liaoning, China
2 Department of Emergency and General, Dalian Stomatological Hospital, 116083 Dalian, Liaoning, China
3 Department of Laboratory Medicine, The Fourth Affiliated Hospital, China Medical University, 110032 Shenyang, Liaoning, China
4 Center of Implant Dentistry, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases, 110002 Shenyang, Liaoning, China
Front. Biosci. (Landmark Ed) 2021, 26(10), 740–751; https://doi.org/10.52586/4984
Submitted: 20 June 2021 | Revised: 9 August 2021 | Accepted: 1 September 2021 | Published: 30 October 2021
Copyright: © 2021 The Author(s). Published by BRI.
This is an open access article under the CC BY 4.0 license (https://creativecommons.org/licenses/by/4.0/).
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
COVID-19
SARS-CoV-2
HNSC
TCGA
Transcript levels
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