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Comparative analysis of SARS-CoV-2 receptor ACE2 expression in multiple solid tumors and matched non-diseased tissues.

ABSTRACT: The emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a global public health emergency. SARS-CoV-2 employs the host cell receptor ACE2 for cellular entry. Nonetheless, the differences in ACE2 expression pattern in lung versus other normal and solid tumor tissues remain incompletely characterized. Here, we analyze a large data set comprising ACE2 mRNA expression for 7592 tissue samples across 22 types of primary solid tumor and 4461 samples across matched 18 non-diseased tissues. Our results unravel eight normal tissues and 10 primary solid tumors, which might be at high risk of SARS-CoV-2 infection. These findings may provide additional insight into the prevention and treatment of SARS-CoV-2 infection, in particular for patients with these 10 vulnerable cancer types.

SUBMITTER: Zhang L

PROVIDER: S-EPMC7301787 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Comparative analysis of SARS-CoV-2 receptor ACE2 expression in multiple solid tumors and matched non-diseased tissues.

Zhang Lei L Han Xiaohong X Shi Yuankai Y

Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases 20200618

The emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a global public health emergency. SARS-CoV-2 employs the host cell receptor ACE2 for cellular entry. Nonetheless, the differences in ACE2 expression pattern in lung versus other normal and solid tumor tissues remain incompletely characterized. Here, we analyze a large data set comprising ACE2 mRNA expression for 7592 tissue samples across 22 types of primary solid tumor and 4461 samples across matched 18 non-diseased ...[more]

PMID: 32565362

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Project description:BACKGROUND:Pandemic COVID-19 by severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) infection is facilitated by the ACE2 receptor and protease TMPRSS2. Modestly sized case series have described clinical factors associated with COVID-19, while ACE2 and TMPRSS2 expression analyses have been described in some cell types. Patients with cancer may have worse outcomes to COVID-19. METHODS:We performed an integrated study of ACE2 and TMPRSS2 gene expression across and within organ systems, by normal versus tumor, across several existing databases (The Cancer Genome Atlas, Census of Immune Single Cell Expression Atlas, The Human Cell Landscape, and more). We correlated gene expression with clinical factors (including but not limited to age, gender, race, body mass index, and smoking history), HLA genotype, immune gene expression patterns, cell subsets, and single-cell sequencing as well as commensal microbiome. RESULTS:Matched normal tissues generally display higher ACE2 and TMPRSS2 expression compared with cancer, with normal and tumor from digestive organs expressing the highest levels. No clinical factors were consistently identified to be significantly associated with gene expression levels though outlier organ systems were observed for some factors. Similarly, no HLA genotypes were consistently associated with gene expression levels. Strong correlations were observed between ACE2 expression levels and multiple immune gene signatures including interferon-stimulated genes and the T cell-inflamed phenotype as well as inverse associations with angiogenesis and transforming growth factor-? signatures. ACE2 positively correlated with macrophage subsets across tumor types. TMPRSS2 was less associated with immune gene expression but was strongly associated with epithelial cell abundance. Single-cell sequencing analysis across nine independent studies demonstrated little to no ACE2 or TMPRSS2 expression in lymphocytes or macrophages. ACE2 and TMPRSS2 gene expression associated with commensal microbiota in matched normal tissues particularly from colorectal cancers, with distinct bacterial populations showing strong associations. CONCLUSIONS:We performed a large-scale integration of ACE2 and TMPRSS2 gene expression across clinical, genetic, and microbiome domains. We identify novel associations with the microbiota and confirm host immunity associations with gene expression. We suggest caution in interpretation regarding genetic associations with ACE2 expression suggested from smaller case series.

Dataset Information

Comparative analysis of SARS-CoV-2 receptor ACE2 expression in multiple solid tumors and matched non-diseased tissues.

Publications

Comparative analysis of SARS-CoV-2 receptor ACE2 expression in multiple solid tumors and matched non-diseased tissues.

Similar Datasets

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