The SARS-CoV-2 host cell receptor ACE2 correlates positively with immunotherapy response and is a potential protective factor for cancer progression

Comput Struct Biotechnol J. 2020:18:2438-2444. doi: 10.1016/j.csbj.2020.08.024. Epub 2020 Sep 2.

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 29 million people and has caused more than 900,000 deaths worldwide as of September 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.

Keywords: ACE2 expression; ACE2, angiotensin-converting enzyme 2; CESC, cervical squamous-cell carcinoma; COAD, colon adenocarcinoma; DFI, disease-free interval; DSS, disease-specific survival; EMT, epithelial-mesenchymal transition; ESCA, esophageal carcinoma; FDR, false discovery rate; GO, gene ontology; GSEA, gene set enrichment analysis; HNSC, head and neck squamous cell carcinoma; KIRC, kidney renal clear cell carcinoma; KIRP, kidney renal papillary cell carcinoma; LUAD, lung adenocarcinoma; LUSC, lung squamous cell carcinoma; OS, overall survival; OV, ovarian carcinoma; PAAD, pancreatic adenocarcinoma; PFI, progression-free interval; Pan-cancer; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; SKCM, skin cutaneous melanoma; Survival prognosis; TCGA, The Cancer Genome Atlas; TF, transcription factor; THYM, thymoma; Tumor immunity and immunotherapy; Tumor progression; UCEC, uterine corpus endometrial carcinoma; WGCNA, weighted gene co-expression network analysis.