Single-Cell Expression Landscape of SARS-CoV-2 Receptor <i>ACE2</i> and Host Proteases in Normal and Malignant Lung Tissues from Pulmonary Adenocarcinoma Patients

Guangchun Han; Ansam Sinjab; Kieko Hara; Warapen Treekitkarnmongkol; Patrick Brennan; Kyle Chang; Elena Bogatenkova; Beatriz Sanchez-Espiridion; Carmen Behrens; Luisa M. Solis; Boning Gao; Luc Girard; Jianjun Zhang; Boris Sepesi; Tina Cascone; Lauren A. Byers; Don L. Gibbons; Jichao Chen; Seyed Javad Moghaddam; Edwin J. Ostrin; Paul Scheet; Junya Fujimoto; Jerry Shay; John V. Heymach; John D. Minna; Steven Dubinett; Ignacio I. Wistuba; Christopher S. Stevenson; Avrum E. Spira; Linghua Wang; Humam Kadara

doi:10.3390/cancers13061250

Cancers (Mar 2021)

Single-Cell Expression Landscape of SARS-CoV-2 Receptor <i>ACE2</i> and Host Proteases in Normal and Malignant Lung Tissues from Pulmonary Adenocarcinoma Patients

Guangchun Han,
Ansam Sinjab,
Kieko Hara,
Warapen Treekitkarnmongkol,
Patrick Brennan,
Kyle Chang,
Elena Bogatenkova,
Beatriz Sanchez-Espiridion,
Carmen Behrens,
Luisa M. Solis,
Boning Gao,
Luc Girard,
Jianjun Zhang,
Boris Sepesi,
Tina Cascone,
Lauren A. Byers,
Don L. Gibbons,
Jichao Chen,
Seyed Javad Moghaddam,
Edwin J. Ostrin,
Paul Scheet,
Junya Fujimoto,
Jerry Shay,
John V. Heymach,
John D. Minna,
Steven Dubinett,
Ignacio I. Wistuba,
Christopher S. Stevenson,
Avrum E. Spira,
Linghua Wang,
Humam Kadara

Affiliations

Guangchun Han: Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Ansam Sinjab: Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Kieko Hara: Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Warapen Treekitkarnmongkol: Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Patrick Brennan: Pathology Department, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Kyle Chang: Guardant Health, Redwood City, CA 94063, USA
Elena Bogatenkova: Pathology Department, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Beatriz Sanchez-Espiridion: Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Carmen Behrens: Department of Thoracic, Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Luisa M. Solis: Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Boning Gao: Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern, Dallas, TX 75390, USA
Luc Girard: Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern, Dallas, TX 75390, USA
Jianjun Zhang: Department of Thoracic, Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Boris Sepesi: Department of Cardiovascular and Thoracic Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77005, USA
Tina Cascone: Department of Thoracic, Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Lauren A. Byers: Department of Thoracic, Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Don L. Gibbons: Department of Thoracic, Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Jichao Chen: Department of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Seyed Javad Moghaddam: Department of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Edwin J. Ostrin: Department of General Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Paul Scheet: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77230, USA
Junya Fujimoto: Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Jerry Shay: Department of Cell Biology, University of Texas Southwestern, Dallas, TX 75390, USA
John V. Heymach: Department of Thoracic, Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
John D. Minna: Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern, Dallas, TX 75390, USA
Steven Dubinett: Department of Medicine, The University of California Los Angeles, Los Angeles, CA 90095, USA
Ignacio I. Wistuba: Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Christopher S. Stevenson: Lung Cancer Initiative at Johnson and Johnson, Cambridge, MA 02142, USA
Avrum E. Spira: Lung Cancer Initiative at Johnson and Johnson, Cambridge, MA 02142, USA
Linghua Wang: Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Humam Kadara: Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA

DOI: https://doi.org/10.3390/cancers13061250
Journal volume & issue: Vol. 13, no. 6
p. 1250

Abstract

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The novel coronavirus SARS-CoV-2 is the causative agent of the COVID-19 pandemic. Severely symptomatic COVID-19 is associated with lung inflammation, pneumonia, and respiratory failure, thereby raising concerns of elevated risk of COVID-19-associated mortality among lung cancer patients. Angiotensin-converting enzyme 2 (ACE2) is the major receptor for SARS-CoV-2 entry into lung cells. The single-cell expression landscape of ACE2 and other SARS-CoV-2-related genes in pulmonary tissues of lung cancer patients remains unknown. We sought to delineate single-cell expression profiles of ACE2 and other SARS-CoV-2-related genes in pulmonary tissues of lung adenocarcinoma (LUAD) patients. We examined the expression levels and cellular distribution of ACE2 and SARS-CoV-2-priming proteases TMPRSS2 and TMPRSS4 in 5 LUADs and 14 matched normal tissues by single-cell RNA-sequencing (scRNA-seq) analysis. scRNA-seq of 186,916 cells revealed epithelial-specific expression of ACE2, TMPRSS2, and TMPRSS4. Analysis of 70,030 LUAD- and normal-derived epithelial cells showed that ACE2 levels were highest in normal alveolar type 2 (AT2) cells and that TMPRSS2 was expressed in 65% of normal AT2 cells. Conversely, the expression of TMPRSS4 was highest and most frequently detected (75%) in lung cells with malignant features. ACE2-positive cells co-expressed genes implicated in lung pathobiology, including COPD-associated HHIP, and the scavengers CD36 and DMBT1. Notably, the viral scavenger DMBT1 was significantly positively correlated with ACE2 expression in AT2 cells. We describe normal and tumor lung epithelial populations that express SARS-CoV-2 receptor and proteases, as well as major host defense genes, thus comprising potential treatment targets for COVID-19 particularly among lung cancer patients.

Published in Cancers

ISSN: 2072-6694 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.mdpi.com/journal/cancers/

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