Pan-cancer analysis reveals that ACE2 is positively associated with immunotherapy response and is a potential protective factor for cancer progression

Zhang, Zhilan; Li, Lin; Li, Mengyuan; Wang, Xiaosheng

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 13 million people and has caused more than 570,000 deaths worldwide as of July 14, 2020. The SARS-CoV-2 human cell receptor ACE2 has recently received extensive attention for its role in SARS-CoV-2 infection. Many studies have also explored the association between ACE2 and cancer. However, a systemic investigation into associations between ACE2 and oncogenic pathways, tumor progression, and clinical outcomes in pan-cancer remains lacking. Using cancer genomics datasets from the Cancer Genome Atlas (TCGA) program, we performed computational analyses of associations between ACE2 expression and antitumor immunity, immunotherapy response, oncogenic pathways, tumor progression phenotypes, and clinical outcomes in 13 cancer cohorts. We found that ACE2 upregulation was associated with increased antitumor immune signatures and PD-L1 expression, and favorable anti-PD-1/PD-L1/CTLA-4 immunotherapy response. ACE2 expression levels inversely correlated with the activity of cell cycle, mismatch repair, TGF-β, Wnt, VEGF, and Notch signaling pathways. Moreover, ACE2 expression levels had significant inverse correlations with tumor proliferation, stemness, and epithelial-mesenchymal transition. ACE2 upregulation was associated with favorable survival in pan-cancer and in multiple individual cancer types. These results suggest that ACE2 is a potential protective factor for cancer progression. Our data may provide potential clinical implications for treating cancer patients infected with SARS-CoV-2.