Int J Biol Sci 2020; 16(15):3028-3036. doi:10.7150/ijbs.51234 This issue

Research Paper

Comprehensive analysis of two potential novel SARS-CoV-2 entries, TMPRSS2 and IFITM3, in healthy individuals and cancer patients

Yu-Jun Dai1,5,6✉*, Wei-Na Zhang3*, Wei-Da Wang1,5,6*, Si-Yuan He4*, Cheng-Cai Liang1,5, Da-Wei Wang2✉

1. Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng East Road, Guangzhou, 510060, China.
2. National Research Center for Translational Medicine, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, 197, Ruijin Road II, Shanghai, 200025, China.
3. Department of Hematology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, China.
4. The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX 77030, USA.
5. State Key Laboratory of Oncology in South China, Guangzhou, 510060, China.
6. Department of Hematologic Oncology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China.
*Co-first authors with equal contributions to this work.

This is an open access article distributed under the terms of the Creative Commons Attribution License ( See for full terms and conditions.
Dai YJ, Zhang WN, Wang WD, He SY, Liang CC, Wang DW. Comprehensive analysis of two potential novel SARS-CoV-2 entries, TMPRSS2 and IFITM3, in healthy individuals and cancer patients. Int J Biol Sci 2020; 16(15):3028-3036. doi:10.7150/ijbs.51234. Available from

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Graphic abstract

Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2, with acute respiratory failure as the most significant symptom, has led to a global pandemic. Angiotensin-converting enzyme 2 (ACE2) is considered as the most important receptor of SARS-CoV-2 and wildly expressed in human tissues. Whereas, the extremely low expression of ACE2 in lung could hardly interpret the severe symptom of pneumonia in COVID-19 patients. Here we profiled two SARS-CoV-2 infection related genes, the transmembrane serine protease 2 (TMPRSS2) and the interferon-inducible transmembrane protein 3 (IFITM3), in human tissues and organs. Consistent with the expression and distribution of ACE2, TMPRSS2 was also highly expressed in digestive, urinary and reproductive systems, but low expressed in lung. Notably, the anti-virus protein IFITM3 also expressed much lower in lung than other tissues, which might be related to the severe lung symptoms of COVID-19. In addition, the low expression of IFITM3 in immune cells suggested that SARS-CoV-2 might attack lymphocytes and induce the cytokine release syndrome (CRS). Furthermore, cancer patients were considered as more susceptible to SARS-CoV-2 infection. Our data supposed that fourteen types of tumors might have different susceptibility to the virus according to ACE2, TMPRSS2 and IFITM3 expression patterns. Interestingly the prognosis of six types of cancers including breast carcinoma (BRCA), lung adenocarcinoma (LUAD), uterine corpus endometrial carcinoma (UCEC), renal clear cell carcinoma (KIRC), prostate adenocarcinoma (PRAD), and hepatocellular carcinoma (LIHC) were closely related to these gene expressions. Our study explored the expression and distribution profiles of two potential novel molecules that might participate in SARS-CoV-2 infection and involved in immunity, which may provide a functional basis for preventing infection of SARS-CoV-2.

Keywords: SARS-CoV-2, Cancer, ACE2, TMPRSS2, IFITM3