TMPRSS2, a SARS-CoV-2 internalization protease is downregulated in head and neck cancer patients

  1. Andrea Sacconi
  2. Sara Donzelli
  3. Claudio Pulito
  4. Stefano Ferrero
  5. Francesca Spinella
  6. Aldo Morrone
  7. Marta Rigoni
  8. Fulvia Pimpinelli
  9. Fabrizio Ensoli
  10. Giuseppe Sanguineti
  11. Raul Pellini
  12. Nishant Agrawal
  13. Evgeny Izumchenko
  14. Gennaro Ciliberto
  15. Aldo Giannì
  16. Paola Muti
  17. Sabrina Strano
  18. Giovanni Blandino

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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 TMPRSS2 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.

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  1. Version published to 10.1186/s13046-020-01708-6
  2. Version published to 10.21203/rs.3.rs-46775/v2 on Research Square
  3. Version published to 10.21203/rs.3.rs-46775/v1 on Research Square
  4. ScreenIT

    SciScore for 10.1101/2020.06.16.154211: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementIACUC: The ethical committee of the Regina Elena National Cancer Institute and of University of Milan approved the study.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Bioinformatic Analysis: Cell cultures: Cal-27 (mutp53H193L) and Detroit-562 (mutp53R175H) cell lines were obtained from ATCC.
    Bioinformatic
    suggested: (QFAB Bioinformatics, RRID:SCR_012513)

    Results from OddPub: Thank you for sharing your data.

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  5. Version published to 10.1101/2020.06.16.154211v1 on bioRxiv