Pan-cancer analysis of RNA expression of ANGIOTENSIN-I-CONVERTING ENZYME 2 reveals high variability and possible impact on COVID-19 clinical outcomes

Abstract

Patients with cancer demonstrate particularly poor outcomes from COVID-19. To provide information essential for understanding the biologic underpinnings of this association, we analyzed whole-transcriptome RNA expression data obtained from a large cohort of cancer patients to characterize expression of ACE2, TMPRSS2, and other proteases that are involved in viral attachment to and entry into target cells. We find substantial variability of expression of these factors across tumor types and identify subpopulations expressing ACE2 at very high levels. In some tumor types, especially in gastrointestinal cancers, expression of ACE2 and TMPRSS2 is highly correlated. Furthermore, we found infiltration with T-cell and natural killer (NK) cell infiltration to be particularly pronounced in ACE2-high tumors. These findings suggest that subsets of cancer patients exist with gene expression profiles that may be associated with heightened susceptibility to SARS-CoV-2 infection, in whom malignant tumors function as viral reservoir and possibly promote the frequently detrimental hyper-immune response in patients infected with this virus.

Comorbidity between lung cancer and COVID-19 pneumonia: role of immunoregulatory gene transcripts in high ACE2-expressing normal lung

“…In conclusion, our work, expanding on prior reports, 5 , 10 , 39 , 40 identified a similar mechanism through which SARS-CoV-2 and tumor cells may interact with the host immune system – the T-cell antigen-mediated immune response. Therefore, our transcriptomic observations may explain a potential comorbidity risk association between the two diseases (NSCLC and COVID-19 pneumonia) and could provide a rationale for new therapeutic strategies .…”

“…These observations are compatible with prior work demonstrating infiltration with T cell and NK cells to be particularly pronounced in ACE2-high tumors. 39 Therefore, subgroups of patients with NSCLC may have gene expression profiles in their normal lung tissue that promote heightened susceptibility to COVID-19 infection and a hyperimmune response. Intriguingly, these correlations between levels of ACE2 transcripts and immune regulatory molecules were not discerned in the tumor tissue.…”