1674MO - ACE2 and TMPRSS2 expression by clinical, HLA, immune, and microbial correlates across 34 human cancers and matched normal tissues: Implications for SARS-CoV-2

Background

Pandemic COVID-19 by SARS-CoV-2 infection is facilitated by the ACE2 receptor and protease TMPRSS2. Patients with cancer may be at particularly high risk for SARS-CoV-2 infection and deleterious outcomes to the disease. A better understanding of potential host risk factors, notably ACE2 and TMPRSS2, in malignant tissues may inform considerations surrounding SARS-CoV-2 and COVID-19 in patients with cancer and more broadly in the general population.

Methods

We performed a large-scale integrated study of ACE2 and TMPRSS2 gene expression in 10,038 patients with cancer across and within organ systems, by normal versus tumor. We investigated its correlative pattern with clinical factors (age, gender, race, BMI and smoking history, etc.), HLA, immune signatures, and commensal microbiome.

Results

Matched normal tissues generally display higher ACE2 and TMPRSS2 expression compared with tumor, with digestive organs expressing the highest levels. No consistent association was observed between clinical groups or HLA genotypes and ACE2/TMPRSS2 levels, after adjusting for tissue-specific expression. ACE2 expression showed a significant correlation with clinically relevant immune signatures including interferon-stimulated genes and the T cell-inflamed phenotype, and with macrophage cell subsets. Single-cell RNAseq analysis demonstrated little to no ACE2 or TMPRSS2 expression in lymphocytes or macrophages. ACE2 and TMPRSS2 showed a distinctive correlative pattern with 75 bacterial taxa in normal tissues particularly from colorectal cancers (gram-negative to positive ratio = 2.6:1). LASSO regression models integrating multi-dimensional correlates revealed immune and microbiota are among the top-ranked features predicting ACE2 expression, while epithelial cell abundance is the dominant predictor for TMPRSS2.

Conclusions

We investigated ACE2 and TMPRSS2 expression across clinical, genetic, immune, and microbiome domains. We identify novel associations with the microbiota and confirm host immunity associations with gene expression. We hope these data may better inform clinical considerations surrounding risk stratification and prevention approaches.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Search Results Web results U.S. Department of Defense.

Disclosure

All authors have declared no conflicts of interest.