Expression of SARS-CoV-2 Related Surface Proteins in Non-Small Cell Lung Cancer Patients and the Influence of Standard of Care Therapy

29 Pages Posted: 25 Feb 2022

See all articles by Christophe Deben

Christophe Deben

University of Antwerp - Center for Oncological Research (CORE)

Maxim Le Compte

affiliation not provided to SSRN

Vasiliki Siozopoulou

affiliation not provided to SSRN

Hilde Lambrechts

affiliation not provided to SSRN

Christophe Hermans

affiliation not provided to SSRN

Ho Wa Lau

affiliation not provided to SSRN

Manon Huizing

University of Antwerp - Antwerp University Hospital (UZA)

Kevin Lamote

affiliation not provided to SSRN

Jeroen M.H. Hendriks

University Hospital Antwerp

Peter van Dam

University of Antwerp

Patrick Pauwels

affiliation not provided to SSRN

Evelien L. J. Smits

affiliation not provided to SSRN

Marc Peeters

University of Antwerp - Multidisciplinary Oncologic Centre Antwerp (MOCA); University of Antwerp - Center for Oncological Research (CORE)

Filip Lardon

affiliation not provided to SSRN

Abstract

Objectives: We aimed to study the expression of SARS-CoV-2-related surface proteins on non-small cell lung cancer (NSCLC) cells and identify clinicopathological characteristics that are related to increased ACE2 protein expression and soluble (s)ACE2 levels with a particular focus on standard of care (SOC) therapies.

Materials and Methods: ACE2 (n=107), TMPRSS2 and FURIN (n=38) protein expression was determined by immunohistochemical (IHC) analysis in NSCLC patients. sACE2 (n=64) were determined in lung cancer patients collected before, during or after treatment with SOC therapies. Finally, ACE2 protein expression was studied in Calu-3 lung cancer spheroids following treatment with SOC therapies.

Results: Membranous (m)ACE2 was co-expressed with mFURIN and/or mTMPRSS2 in 16% of the NSCLC samples and limited to the adenocarcinoma subtype. TMPRSS2 showed predominantly atypical cytoplasmic expression. mACE2 and sACE2 was more frequently expressed in mutant EGFR patients, but not mutant KRAS patients. Similarly, ACE2 mRNA expression was increased in EGFR mutant TCGA LUAD tumors and positively correlated with ERBB2-4 expression, while ACE2 expression was lower in KRAS mutant patients and inversely correlated with KRAS, NRAS and HRAS expression levels. Importantly, neoadjuvant chemotherapy was not associated with increased mACE2 expression levels. A significant difference was observed in sACE2 for patients treated with targeted therapies, but not for chemo- and immunotherapy. Finally, paradoxical MAPK activation by Dabrafenib, and Buparlisib- and Crizotinib-dependent PI3K inhibition reduced ACE2 expression in Calu-3 lung cancer spheroids.

Conclusion: We identified a role for mutation dependent PI3K pathway activation in the expression of mACE2 on NSCLC cells, associated with increased sACE2 levels in patients. Therefore, it is of high interest to study SARS-CoV-2 infected EGFR, ALK, ROS1 and cMET mutated NSCLC patients more in depth to get a better understanding on how mACE2, sACE2 and SOC TKIs can affect the course of COVID-19.

Note:
Funding Information: This was work supported by two “Kom Op Tegen Kanker” grants (ref 000100470, KotK_UA/2020/12228/1), a “Bijzonder Onderzoeksfonds COVID19-Project” grant (project ID: 42839) and a UZA Foundation grant.

Conflict of Interests: The authors declare no conflict of interest.

Ethical Approval: This retrospective study has been approved by the Ethics Committee of the Antwerp University Hospital/University of Antwerp (EC number 20/22/278).

Keywords: SARS-CoV-2, ACE2, Lung cancer

Suggested Citation

Deben, Christophe and Le Compte, Maxim and Siozopoulou, Vasiliki and Lambrechts, Hilde and Hermans, Christophe and Lau, Ho Wa and Huizing, Manon and Lamote, Kevin and Hendriks, Jeroen M.H. and van Dam, Peter and Pauwels, Patrick and Smits, Evelien L. J. and Peeters, Marc and Lardon, Filip, Expression of SARS-CoV-2 Related Surface Proteins in Non-Small Cell Lung Cancer Patients and the Influence of Standard of Care Therapy. Available at SSRN: https://ssrn.com/abstract=4043413 or http://dx.doi.org/10.2139/ssrn.4043413

Christophe Deben (Contact Author)

University of Antwerp - Center for Oncological Research (CORE) ( email )

Drie Eikenstraat 655
Edegem, 2650
Belgium

Maxim Le Compte

affiliation not provided to SSRN ( email )

No Address Available

Vasiliki Siozopoulou

affiliation not provided to SSRN ( email )

No Address Available

Hilde Lambrechts

affiliation not provided to SSRN ( email )

No Address Available

Christophe Hermans

affiliation not provided to SSRN ( email )

No Address Available

Ho Wa Lau

affiliation not provided to SSRN ( email )

No Address Available

Manon Huizing

University of Antwerp - Antwerp University Hospital (UZA) ( email )

Edegem
Belgium

Kevin Lamote

affiliation not provided to SSRN ( email )

No Address Available

Jeroen M.H. Hendriks

University Hospital Antwerp ( email )

Edegem
Belgium

Peter Van Dam

University of Antwerp ( email )

Prinsstraat 13
Antwerp, 2000
Belgium

Patrick Pauwels

affiliation not provided to SSRN ( email )

No Address Available

Evelien L. J. Smits

affiliation not provided to SSRN ( email )

No Address Available

Marc Peeters

University of Antwerp - Multidisciplinary Oncologic Centre Antwerp (MOCA) ( email )

Antwerp University Hospital
Drie Eikenstraat 655
Edegem, 2650
Belgium
+323 821 43 66 (Phone)

University of Antwerp - Center for Oncological Research (CORE)

Drie Eikenstraat 655
Edegem, 2650
Belgium

Filip Lardon

affiliation not provided to SSRN ( email )

No Address Available

Do you have negative results from your research you’d like to share?

Paper statistics

Downloads
72
Abstract Views
267
Rank
585,331
PlumX Metrics