High expression of ACE2 in HER2 subtype of breast cancer is a marker of poor prognosis

Abstract

BackgroundACE2 a key molecule of the Renin-Angiotensin system has been identified as the receptor for SARS-CoV-2 entry into human cells. In the context of human cancers, there is evidence that ACE2 might function as a tumor suppressor. The expression levels of ACE2 among the different subtypes of breast cancer has not been investigated. MethodsWe have examined the differential expression of ACE2 and its correlation with prognosis in breast cancer subtypes using the METABRIC (n = 1898) and TCGA (n = 832) cohorts. Correlations were evaluated by Pearsons's correlation co-efficient and Kaplan-Meier analysis was used to estimate differences in disease-free survival between the ACE2 high and ACE2 low groups. ResultsThere is minimal expression of ACE2 in the luminal classes, but significantly higher levels in the Basal-like and HER2-enriched subclasses. Metastatic biopsies of these tumor types also show enhanced expression of ACE2. High levels of ACE2 correlated with decreased disease-free survival in the HER2-enriched subtype, and it was positively correlated with EGFR expression. ConclusionThese observations suggest ACE2 might function as a context dependent factor driving tumor progression in breast cancer and permit new opportunities for targeted therapy.