Genetic alteration, RNA expression, and DNA methylation profiling of coronavirus disease 2019 (COVID-19) receptor ACE2 in malignancies: a pan-cancer analysis

Abstract

The novel coronavirus (2019-nCoV) is an emerging causative agent that was first described in late December 2019 and causes a severe respiratory infection in humans. Notably, many of affected patients of COVID-19 were people with malignancies. Moreover, cancer has been identified as an individual risk factor for COVID-19. In addition, the expression of angiotensin converting enzyme 2 (ACE2), the receptor of COVID-19, were aberrantly expressed in many tumors. However, a systematic analysis of ACE2 aberration remained to be elucidated in human cancers. Here, we analyzed genetic alteration, RNA expression, and DNA methylation of ACE2 across over 30 tumors. Notably, overexpression of ACE2 have been observed in including colon adenocarcinoma (COAD), kidney renal papillary cell carcinoma (KIRP), pancreatic adenocarcinoma (PAAD), rectum adenocarcinoma (READ), stomach adenocarcinoma (STAD), and lung adenocarcinoma (LUAD). In addition, hypo DNA methylation of ACE2 has also been identified in most of these ACE2 highly expressed tumors. Conclusively, our study for the first time curated both genetic and epigenetic variations of ACE2 in human malignancies. Notably, because our study is a bioinformatics assay, further functional and clinical validation is warranted.

Keywords: ACE2; COVID-19; Expression.

Fig. 1

RNA expression aberration of ACE2 in tumors. a RNA expression aberration of ACE2 in tumors using GEPIA2 (upper panel) and Ualcan (lower panel) database. Red, tumor samples; grey, normal control samples. b Colon adenocarcinoma (COAD), kidney renal papillary cell carcinoma (KIRP), pancreatic adenocarcinoma (PAAD), rectum adenocarcinoma (READ), lung adenocarcinoma (LUAD), and stomach adenocarcinoma (STAD) presented increased ACE2 expression. *p < 0.05. This data was obtained using GEPIA2. Red, tumor samples; grey, normal control samples. c Testicular germ cell tumors (TGCT), thyroid carcinoma (THCA), and kidney chromophobe (KICH) presented decreased ACE2 expression. *p < 0.05. This data was obtained using GEPIA2. Red, tumor samples; grey, normal control samples.

Fig. 2

DNA methylation aberration of ACE2 in tumors. a Probes for detecting DNA methylation of ACE2 promoter. b Four highly ACE2 express tumors presented with decreased DNA methylation level of ACE2, including colon adenocarcinoma (COAD), kidney renal papillary cell carcinoma (KIRP), pancreatic adenocarcinoma (PAAD), and rectum adenocarcinoma (READ). *p < 0.05. This data was obtained using Ualcan. c An ACE2 downregulated tumor, testicular germ cell tumors (TGCT), presented increased DNA methylation level. *p < 0.05. This data was obtained using Ualcan.