Identification of key factors shaping integrated levels of ACE2 and TMPRSS2 expression in head and neck squamous cell carcinoma

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

^*Correspondence: xyan@cmu.edu.cn (Xu Yan); zhangxinwen@cmu.edu.cn (Xinwen Zhang)

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

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

Figures

Fig. 1.

Previous article in this issue

Next article in this issue

Fig. 1.

Distribution of both ACE2 and TMPRSS2 levels, and TPSI scores in normal and tumor tissues across 11 tumor types in TCGA. ${}^{*}$ p $<$ 0.05, ${}^{**}$ p $<$ 0.01, ${}^{***}$ p $<$ 0.001, ${}^{****}$ p $<$ 0.0001.

1 of 6

Front. Biosci. (Landmark Ed) Print ISSN 2768-6701 Electronic ISSN 2768-6698