Han Guangchun, Sinjab Ansam, Hara Kieko, Treekitkarnmongkol Warapen, Brennan Patrick, Chang Kyle, Bogatenkova Elena, Sanchez-Espiridion Beatriz, Behrens Carmen, Solis Luisa M, Gao Boning, Girard Luc, Zhang Jianjun, Sepesi Boris, Cascone Tina, Byers Lauren A, Gibbons Don L, Chen Jichao, Moghaddam Seyed Javad, Ostrin Edwin J, Scheet Paul, Fujimoto Junya, Shay Jerry, Heymach John V, Minna John D, Dubinett Steven, Wistuba Ignacio I, Stevenson Christopher S, Spira Avrum E, Wang Linghua, Kadara Humam
Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Cancers (Basel). 2021 Mar 12;13(6):1250. doi: 10.3390/cancers13061250.
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 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 and other SARS-CoV-2-related genes in pulmonary tissues of lung adenocarcinoma (LUAD) patients. We examined the expression levels and cellular distribution of and SARS-CoV-2-priming proteases and 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 , , and . Analysis of 70,030 LUAD- and normal-derived epithelial cells showed that levels were highest in normal alveolar type 2 (AT2) cells and that was expressed in 65% of normal AT2 cells. Conversely, the expression of was highest and most frequently detected (75%) in lung cells with malignant features. -positive cells co-expressed genes implicated in lung pathobiology, including COPD-associated , and the scavengers and . Notably, the viral scavenger was significantly positively correlated with 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.
新型冠状病毒SARS-CoV-2是COVID-19大流行的病原体。有严重症状的COVID-19与肺部炎症、肺炎和呼吸衰竭相关，因此引发了对肺癌患者中COVID-19相关死亡率升高风险的担忧。血管紧张素转换酶2（ACE2）是SARS-CoV-2进入肺细胞的主要受体。肺癌患者肺组织中ACE2及其他与SARS-CoV-2相关基因的单细胞表达情况仍不清楚。我们试图描绘肺腺癌（LUAD）患者肺组织中ACE2及其他与SARS-CoV-2相关基因的单细胞表达谱。我们通过单细胞RNA测序（scRNA-seq）分析检测了5例LUAD和14例匹配的正常组织中ACE2、SARS-CoV-2启动蛋白酶TMPRSS2和CTSL的表达水平及细胞分布。对186,916个细胞进行的scRNA-seq显示了ACE2、TMPRSS2和CTSL的上皮特异性表达。对70,030个LUAD和正常来源的上皮细胞分析表明，ACE2水平在正常肺泡2型（AT2）细胞中最高，且65%的正常AT2细胞表达ACE2。相反，TMPRSS2的表达在具有恶性特征的肺细胞中最高且最常被检测到（75%）。ACE2阳性细胞共表达了与肺病理生物学相关的基因，包括与慢性阻塞性肺疾病（COPD）相关的SPINK1，以及清道夫蛋白SCGB1A1和LYZ。值得注意的是，病毒清道夫蛋白LYZ与AT2细胞中的ACE2表达显著正相关。我们描述了表达SARS-CoV-2受体和蛋白酶以及主要宿主防御基因的正常和肿瘤肺上皮细胞群体，因此这些群体构成了COVID-19潜在的治疗靶点，尤其是在肺癌患者中。
