TMPRSS2, a SARS-CoV-2 internalization protease is downregulated in head and neck cancer patients
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(2020) 39:200
RESEARCH
Open Access
TMPRSS2, a SARS-CoV-2 internalization protease is downregulated in head and neck cancer patients Andrea Sacconi1, Sara Donzelli2, Claudio Pulito2, Stefano Ferrero3,4, Francesca Spinella5, Aldo Morrone6, Marta Rigoni3,7, Fulvia Pimpinelli8, Fabrizio Ensoli8, Giuseppe Sanguineti9, Raul Pellini10, Nishant Agrawal11, Evgeny Izumchenko12, Gennaro Ciliberto13, Aldo Giannì3,4, Paola Muti3, Sabrina Strano14 and Giovanni Blandino1*
Abstract Background: SARS-coronavirus-2 enters host cells through binding of the Spike protein to ACE2 receptor and subsequent S priming by the TMPRSS2 protease. We aim to assess differences in both ACE2 and TMPRSS2 expression in normal tissues from oral cavity, pharynx, larynx and lung tissues as well as neoplastic tissues from the same areas. Methods: The study has been conducted using the TCGA and the Regina Elena Institute databases and validated by experimental model in HNSCC cells. We also included data from one COVID19 patient who went under surgery for HNSCC. Results: TMPRSS2 expression in HNSCC was significantly reduced compared to the normal tissues. It was more evident in women than in men, in TP53 mutated versus wild TP53 tumors, in HPV negative patients compared to HPV positive counterparts. Functionally, we modeled the multivariate effect of TP53, HPV, and other inherent variables on TMPRSS2. All variables had a statistically significant independent effect on TMPRSS2. In particular, in tumor tissues, HPV negative, TP53 mutated status and elevated TP53-dependent Myc-target genes were associated with low TMPRSS2 expression. The further analysis of both TCGA and our institutional HNSCC datasets identified a signature anti-correlated to TMPRSS2. As proof-of-principle we also validated the anti-correlation between microRNAs and TMPRSS2 expression in a SARS-CoV-2 positive HNSCC patient tissues Finally, we did not find TMPR SS2 promoter methylation. Conclusions: Collectively, these findings suggest that tumoral tissues, herein exemplified by HNSCC and lung cancers might be more resistant to SARS-CoV-2 infection due to reduced expression of TMPRSS2. These observations may help to better assess the frailty of SARS-CoV-2 positive cancer patients. Keywords: SARS-CoV-2, TMPRSS2, HNSCC, microRNAs TP53, MYC
* Correspondence: [email protected] 1 UOSD Clinical Trial Center, Biostatistics and Bioinformatics, IRCCS Regina Elena National Cancer Institute, Rome, Italy Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in
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