Abstract 702: Single-cell expression landscape of SARS-CoV-2 receptorACE2and host proteases in human lung adenocarcinoma

Abstract

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-asociated mortality among lung cancer patients. Angiotensin converting enzyme 2 (ACE2) is the major receptor for SARS-CoV-2 entry into lung cells. Yet, the single-cell expression landscape of ACE2 and other SARS-CoV-2-related genes in pulmonary tissues of lung cancer patients remains unknown. To fill these voids, we leveraged our ongoing efforts in single-cell transcriptomic analysis of 186,916 cells including a large number of epithelial cells (n=70,030) derived from 5 LUADs and 14 matching uninvolved normal lung tissues, to delineate expression levels and cellular distribution of ACE2 and SARS-CoV-2 priming proteases TMPRSS2 and TMPRSS4. Single-cell RNA sequencing 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, expression of TMPRSS4 was highest and most frequently detected (75%) in malignant lung cells. 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. In conclusion, we describe normal and tumor lung epithelial populations that express SARS-CoV-2 receptor and proteases, as well as major host defense genes, and that thus comprise potential treatment targets for COVID-19 particularly among lung cancer patients. Citation Format: Guangchun Han, Ansam Sinjab, Kieko Hara, Warapen Treekitkarnmongkol, Patrick Brennan, Kyle Chang, Elena Bokatenkova, 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. Single-cell expression landscape of SARS-CoV-2 receptor ACE2 and host proteases in human lung adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 702.