Pan-cancer analysis of transmembrane protease serine 2 and cathepsin L that mediate cellular SARS-CoV-2 infection leading to COVID-19

Periklis Katopodis

Vladimir Anikin

Harpal Randeva

Demetrios Spandidos

Kamaljit Chatha

Ioannis Kyrou

Emmanouil Karteris

^{Biosciences, College of Health and Life Sciences, Brunel University London, Uxbridge UB8 3PH}

^{Division of Thoracic Surgery, The Royal Brompton and Harefield NHS Foundation Trust, Harefield Hospital, London UB9 6JH, UK}

^{Department of Oncology and Reconstructive Surgery, Sechenov First Moscow State Medical University, 119146 Moscow, Russia}

^{Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals Coventry and Warwickshire NHS Trust, Coventry CV2 2DX}

^{Aston Medical Research Institute, Aston Medical School, Aston University, Birmingham B4 7ET}

^{Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK}

^{Laboratory of Clinical Virology, School of Medicine, University of Crete, 71003 Heraklion, Greece}

^{Department of Biochemistry and Immunology, University Hospitals Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, UK}

Correspondence to: Dr Emmanouil Karteris, Biosciences, College of Health and Life Sciences, Brunel University London, Uxbridge UB8 3PH, UK E-mail: ku.ca.lenurb@siretrak.liuonamme

^{Joint senior authorship}

Received 2020 May 11; Accepted 2020 May 26.

This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Abstract

Severe acute respiratory syndrome (SARS) coronavirus-2 (SARS-CoV2) is the cause of a new disease (COVID-19) which has evolved into a pandemic during the first half of 2020. Older age, male sex and certain underlying diseases, including cancer, appear to significantly increase the risk for severe COVID-19. SARS-CoV-2 infection of host cells is facilitated by the angiotensin-converting enzyme 2 (ACE-2), and by transmembrane protease serine 2 (TMPRSS2) and other host cell proteases such as cathepsin L (CTSL). With the exception of ACE-2, a systematic analysis of these two other SARS-CoV2 infection mediators in malignancies is lacking. Here, we analysed genetic alteration, RNA expression, and DNA methylation of TMPRSS2 and CTSL across a wide spectrum of tumors and controls. TMPRSS2 was overexpressed in cervical squamous cell carcinoma and endocervical adenocarcinoma, colon adenocarcinoma, prostate adenocarcinoma (PRAD), rectum adenocarcinoma (READ), uterine corpus endometrial carcinoma and uterine carcinosarcoma, with PRAD and READ exhibiting the highest expression of all cancers. CTSL was upregulated in lymphoid neoplasm diffuse large B-cell lymphoma, oesophageal carcinoma, glioblastoma multiforme, head and neck squamous cell carcinoma, lower grade glioma, pancreatic adenocarcinoma, skin cutaneous melanoma, stomach adenocarcinoma, and thymoma. Hypo-methylation of both genes was evident in most cases where they have been highly upregulated. We have expanded on our observations by including data relating to mutations and copy number alterations at pan-cancer level. The novel hypotheses that are stemming out of these data need to be further investigated and validated in large clinical studies.

Keywords: cathepsin L (CTSL), transmembrane protease serine 2 (TMPRSS2), pan-cancer, DNA methylation, COVID-19, angiotensin-converting enzyme 2

Abstract

Acknowledgments

Not applicable.

Acknowledgments

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