Pan-cancer analysis of RNA expression of ANGIOTENSIN-I-CONVERTING ENZYME 2 reveals high variability and possible impact on COVID-19 clinical outcomes.


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
11 03 2021
Historique:
received: 26 07 2020
accepted: 17 02 2021
entrez: 12 3 2021
pubmed: 13 3 2021
medline: 20 3 2021
Statut: epublish

Résumé

Patients with cancer demonstrate particularly poor outcomes from COVID-19. To provide information essential for understanding the biologic underpinnings of this association, we analyzed whole-transcriptome RNA expression data obtained from a large cohort of cancer patients to characterize expression of ACE2, TMPRSS2, and other proteases that are involved in viral attachment to and entry into target cells. We find substantial variability of expression of these factors across tumor types and identify subpopulations expressing ACE2 at very high levels. In some tumor types, especially in gastrointestinal cancers, expression of ACE2 and TMPRSS2 is highly correlated. Furthermore, we found infiltration with T-cell and natural killer (NK) cell infiltration to be particularly pronounced in ACE2-high tumors. These findings suggest that subsets of cancer patients exist with gene expression profiles that may be associated with heightened susceptibility to SARS-CoV-2 infection, in whom malignant tumors function as viral reservoir and possibly promote the frequently detrimental hyper-immune response in patients infected with this virus.

Identifiants

pubmed: 33707526
doi: 10.1038/s41598-021-84731-7
pii: 10.1038/s41598-021-84731-7
pmc: PMC7952699
doi:

Substances chimiques

RNA 63231-63-0
ACE2 protein, human EC 3.4.17.23
Angiotensin-Converting Enzyme 2 EC 3.4.17.23
Serine Endopeptidases EC 3.4.21.-
TMPRSS2 protein, human EC 3.4.21.-

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

5639

Références

Nature. 2020 Mar;579(7798):270-273
pubmed: 32015507
Cancer Discov. 2020 Jun;10(6):783-791
pubmed: 32345594
Med Hypotheses. 2020 Oct;143:109893
pubmed: 32512290
MMWR Morb Mortal Wkly Rep. 2020 Apr 17;69(15):458-464
pubmed: 32298251
Cell. 2020 Apr 16;181(2):281-292.e6
pubmed: 32155444
Front Immunol. 2019 Aug 06;10:1842
pubmed: 31447850
Proc Natl Acad Sci U S A. 2020 Jan 14;117(2):1119-1128
pubmed: 31888983
PLoS Pathog. 2020 Apr 28;16(4):e1008520
pubmed: 32343745
J Hematol Oncol. 2020 May 4;13(1):43
pubmed: 32366279
Lancet Infect Dis. 2020 May;20(5):533-534
pubmed: 32087114
Proc Natl Acad Sci U S A. 2020 May 26;117(21):11727-11734
pubmed: 32376634
Lung Cancer. 2020 Aug;146:19-22
pubmed: 32505076
Clin Sci (Lond). 2014 Aug;127(4):243-9
pubmed: 24564768
Int J Oncol. 2020 Aug;57(2):533-539
pubmed: 32468052
J Cell Mol Med. 2020 Aug;24(16):9478-9482
pubmed: 32639084
Lancet Oncol. 2020 Mar;21(3):335-337
pubmed: 32066541
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
Mol Ther. 2017 May 3;25(5):1107-1116
pubmed: 28392162
Genome Biol. 2016 Dec 1;17(1):249
pubmed: 27908289
Mol Cancer. 2020 Apr 28;19(1):80
pubmed: 32345328
J Clin Invest. 2018 Feb 1;128(2):876-889
pubmed: 29355843
Nucleic Acids Res. 2000 Jan 1;28(1):27-30
pubmed: 10592173
Nat Methods. 2017 Apr;14(4):417-419
pubmed: 28263959
Cell. 2020 Apr 16;181(2):271-280.e8
pubmed: 32142651
Int J Oral Sci. 2020 Feb 24;12(1):8
pubmed: 32094336
Nat Rev Nephrol. 2018 May;14(5):325-336
pubmed: 29578208
J Autoimmun. 2020 Aug;112:102463
pubmed: 32303424
Am J Physiol Lung Cell Mol Physiol. 2009 Jul;297(1):L84-96
pubmed: 19411314
J Virol. 2009 Jul;83(14):7062-74
pubmed: 19420084
Cell. 2020 May 14;181(4):894-904.e9
pubmed: 32275855
J Pathol. 2006 Nov;210(3):288-97
pubmed: 17031779

Auteurs

Andrew Elliott (A)

Caris Life Sciences, 4610 South 44th Place, Phoenix, AZ, 85040, USA.

Michelle Saul (M)

Caris Life Sciences, 4610 South 44th Place, Phoenix, AZ, 85040, USA.

Jia Zeng (J)

Caris Life Sciences, 4610 South 44th Place, Phoenix, AZ, 85040, USA.

John L Marshall (JL)

Ruesch Center for the Cure of Gastrointestinal Cancers, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA.

Edward S Kim (ES)

Levine Cancer Institute, Atrium Health, Charlotte, NC, USA.

Misako Nagasaka (M)

Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA.

Heinz-Josef Lenz (HJ)

University of Southern California, Keck School of Medicine, Norris Comprehensive Cancer Center, Los Angeles, CA, USA.

Lee Schwartzberg (L)

Medical Oncology, West Cancer Center, 9745 Wolf River Blvd, Germantown, TN, USA.

David Spetzler (D)

Caris Life Sciences, 4610 South 44th Place, Phoenix, AZ, 85040, USA.

Jim Abraham (J)

Caris Life Sciences, 4610 South 44th Place, Phoenix, AZ, 85040, USA.

Joanne Xiu (J)

Caris Life Sciences, 4610 South 44th Place, Phoenix, AZ, 85040, USA.

Phillip Stafford (P)

Caris Life Sciences, 4610 South 44th Place, Phoenix, AZ, 85040, USA.

W Michael Korn (W)

Caris Life Sciences, 4610 South 44th Place, Phoenix, AZ, 85040, USA. wmkorn@carisls.com.
Division of Hematology/Oncology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA. wmkorn@carisls.com.

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Classifications MeSH