Systematic profiling of ACE2 expression in diverse physiological and pathological conditions for COVID-19/SARS-CoV-2

Abstract

Recent retrospective studies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) revealed that the patients with common comorbidities of cancers and chronic diseases face significantly poorer clinical outcomes than those without. Since the expression profile of ACE2, a crucial cell entry receptor for SARS-CoV-2, could indicate the susceptibility to SARS-CoV-2 infection, here we systematically dissected ACE2 expression using large-scale multi-omics data from 30 organs/tissues, 33 cancer types and some common chronic diseases involving >28 000 samples. It was found that sex and age could be correlated with the susceptibility of SARS-CoV-2 infection for certain tissues. Strikingly, ACE2 was up-regulated in cervical squamous cell carcinoma and endocervical adenocarcinoma, colon adenocarcinoma, oesophageal carcinoma, kidney renal papillary cell carcinoma, lung adenocarcinoma and uterine corpus endometrial carcinoma compared to controls. Furthermore, the patients with common chronic diseases regarding angiocardiopathy, type 2 diabetes, liver, pneumonia and hypertension were also with higher ACE2 expression compared to related controls, which were validated using independent data sets. Collectively, our study may reveal a novel important mechanism that the patients with certain cancers and chronic diseases may express higher ACE2 expression compared to the individuals without diseases, which could lead to their higher susceptibility to multi-organ injury of SARS-CoV-2 infection.

Keywords: ACE2; COVID-19; SARS-CoV-2; gene expression.

FIGURE 1

Expression and regulation of ACE2 in diverse normal tissues and cancers. A, Boxplot showing ACE2 expression in 30 different organs/tissues from GTEx project. B, ACE2 Expression differences between sexes in tissues. C, Boxplot displaying ACE2 expression comparison between distinct age groups. D, Transcription factor regulatory network for ACE2 in different tissues. Green nodes represent the detected transcription factors regulating ACE2. The intensity of the colour for tissues denotes the averaged expression level ACE2 in corresponding tissues. E, Boxplot displaying the up‐regulation of ACE2 in related cancers. F, Expression comparison between males and females in cancers. G, DNA methylation level comparison between males and females for ACE2 in tumours. H, Transcription factor regulatory network for ACE2 in cancers. Green nodes denote the detected transcription factors regulating ACE2. The intensity of the colour for cancers stands for the averaged expression level ACE2 in corresponding cancers. Note: Student's t test was used to check the significance. CESC, cervical squamous cell carcinoma and endocervical adenocarcinoma; COAD, colon adenocarcinoma; ESCA, oesophageal carcinoma; KIRP, kidney renal papillary cell carcinoma; LUAD, lung adenocarcinoma; UCEC, uterine corpus endometrial carcinoma; BLCA, bladder urothelial carcinoma; HNSC, head and neck squamous cell carcinoma; KIRC, kidney renal clear cell carcinoma; THCA, thyroid carcinoma; STAD, stomach adenocarcinoma; PAAD, pancreatic adenocarcinoma; CHOL, cholangiocarcinoma

FIGURE 2

Expression profile of ACE2 in common chronic diseases. A, Expression comparison of ACE2 in cardiovascular diseases. Left (GSE29819): ACRV represents arrhythmogenic right ventricular cardiomyopathy; DCM denotes idiopathic dilated cardiomyopathy. Middle (GSE26887): Normal heart and heart failure with and without T2D. Right (GSE59867). B, Boxplot showing expression comparison of ACE2 in diabetes‐related data sets. Left (GSE25724); middle (GSE23343); right (GSE77962): abdominal subcutaneous white adipose tissue of overweight, weight loss and weight stable period. C, Expression comparison of ACE2 in chronic liver diseases. Left (GSE6764); middle (GSE14323); right (GSE89632). D, Expression comparison of ACE2 in pneumonia‐related diseases. Left (GSE10667); middle (GSE42830); right (GSE110147). E. Boxplot displaying expression comparison of ACE2 in hypertension‐related diseases. Left (GSE53408); right (GSE113439). Note: Student's t test was employed to examine the significance