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Integrated Bioinformatic Analysis of SARS-CoV-2 Infection Related Genes ACE2, BSG and TMPRSS2 in Aerodigestive Cancers

Authors He C, Hua X, Sun S, Li S, Wang J, Huang X

Received 8 January 2021

Accepted for publication 23 February 2021

Published 10 March 2021 Volume 2021:14 Pages 791—802


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Professor Ning Quan

Chaobin He,1– 3,* Xin Hua,1,2,4,* Shuxin Sun,1– 3,* Shaolong Li,1,2 Jun Wang,1– 3 Xin Huang1– 3

1Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, People’s Republic of China; 2Department of Experimental Research, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People’s Republic of China; 3Department of Pancreatobiliary Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People’s Republic of China; 4Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Xin Huang
Department of Pancreatobiliary Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, People’s Republic of China
Email [email protected]

Background: Cancer patients are more vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection than the general population, with lung epithelial cells or enterocytes being the main targets. However, the expressions of SARS-CoV-2 entry-related genes in aerodigestive cancers have not been fully elucidated.
Methods: In this study, the expressions of SARS-CoV-2 receptors and cofactors, including angiotensin I-converting enzyme 2 (ACE2), basigin (BSG) and transmembrane serine protease 2 (TMPRSS2), were comprehensively assessed. We compared BSG and TMPRSS2 expressions between aerodigestive cancers and matched normal tissues through Gene Expression Profiling Interactive Analysis 2 (GEPIA2). Furthermore, expressions in healthy colon tissues at different anatomical locations were explored using the Genotype-Tissue Expression (GTEx) dataset. In addition, expressions among different tumor stages and the prognostic values were detected through GEPIA2. Moreover, the correlation between gene expression and immune infiltration was explored via Tumor Immune Estimation Resource (TIMER). Finally, expressions in primary colorectal cancer (CRC), lung metastasis and liver metastasis were investigated using the Gene Expression Omnibus (GEO) dataset GSE41258.
Results: Similar to ACE2, TMPRSS2 and BSG were also highly expressed in the digestive tracts. Intriguingly, BSG/TMPRSS2 expression in adjacent normal colon tissue or lung tissue was higher than that in corresponding healthy tissue, whereas they varied not among different tumor stages and correlated not with prognosis in aerodigestive cancers. Moreover, ACE2 was expressed at higher levels in lung metastases from CRC than in normal lung tissues.
Conclusion: SARS-CoV-2 entry genes were highly expressed in CRC, and we reported for the first time higher expression of ACE2 in lung metastases from CRC than in normal lung, indicating that these patients may be more susceptible to extrapulmonary or pulmonary SARS-CoV-2 infection. Since our study is a bioinformatic analysis, further experimental evidences and clinical data are urgently needed.

Keywords: ACE2, BSG, TMPRSS2, COVID-19, aerodigestive cancers

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