Int J Biol Sci 2021; 17(8):1925-1939. doi:10.7150/ijbs.57802

Research Paper

Downregulation of ACE2 expression by SARS-CoV-2 worsens the prognosis of KIRC and KIRP patients via metabolism and immunoregulation

Qian Tang1,3*, Yue Wang2*, Ling Ou4, Jieling Li2, Kai Zheng2, Hui Zhan3, Jiayu Gu3, Guibao Zhou3, Shouxia Xie3, Jianping Zhang1, Wei Huang4✉, Shaoxiang Wang2✉, Xiao Wang1,3✉

1. School of Pharmacy, Jinan University, Guangzhou 510630, China.
2. School of Pharmaceutical Sciences, Shenzhen University Health Science Center, Shenzhen 518000, China.
3. Department of Pharmacy, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, China.
4. Bacteriology & Antibacterial Resistance Surveillance Laboratory, Shenzhen Institute of Respiratory Diseases, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, China.
*These authors contributed equally to this work.

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Citation:
Tang Q, Wang Y, Ou L, Li J, Zheng K, Zhan H, Gu J, Zhou G, Xie S, Zhang J, Huang W, Wang S, Wang X. Downregulation of ACE2 expression by SARS-CoV-2 worsens the prognosis of KIRC and KIRP patients via metabolism and immunoregulation. Int J Biol Sci 2021; 17(8):1925-1939. doi:10.7150/ijbs.57802. Available from https://www.ijbs.com/v17p1925.htm

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Abstract

Background: Angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) allow entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into host cells and play essential roles in cancer therapy. However, the functions of ACE2 and TMPRSS2 in kidney cancer remain unclear, especially as kidneys are targets for SARS-CoV-2 infection.

Methods: UCSC Xena project, the Cancer Genome Atlas (TCGA), and Gene Expression Omnibus (GEO) databases (GSE30589 and GSE59185) were searched for gene expression in human tissues, gene expression data, and clinical information. Several bioinformatics methods were utilized to analyze the correlation between ACE2 and TMPRSS2 with respect to the prognosis of kidney renal clear cell carcinoma (KIRC) and kidney renal papillary cell carcinoma (KIRP).

Results: ACE2 expression was significantly upregulated in tumor tissue, while its downregulation was associated with low survival in KIRC and KIRP patients. TMPRSS2 was downregulated in KIRC and KIRP, and its expression was not correlated with patient survival. According to clinical risk factor-based prediction models, ACE2 exhibits predictive accuracy for kidney cancer prognosis and is correlated with metabolism and immune infiltration. In an animal model, ACE2 expression was remarkably downregulated in SARS-CoV-2-infected cells compared to in the control.

Conclusion: ACE2 expression is highly correlated with various metabolic pathways and is involved in immune infiltration.it plays a crucial role than TMPRSS2 in diagnosing and prognosis of kidney cancer patients. The overlap in ACE2 expression between kidney cancer and SARS-CoV-2 infection suggests that patients with KIRC or KIRP are at high risk of developing serious symptoms.

Keywords: ACE2, TMPRSS2, renal cancer, SARS-CoV-2, overall survival