The Abnormal ACE2 Expression Correlated with Immune Infiltration May Worsen Progression After SARS-CoV-2 Infection in UCEC and KIRP

Background: ACE2 is a receptor for SARS-CoV-2 entry into cells. However, the related prognosis and possible immune mechanisms of ACE2 in UCEC and KIRP after SARS-CoV-2 infection are still ambiguous. Objectives: We aim to explore the correlation of ACE2 with immune infiltration and progression in UCEC and KIRP after SARS-CoV-2 infection. Methods: We analyzed the expression levels of ACE2 in different tumors in oncomine and TIMER databases, and used the PrognoScan, GEPIA and Kaplan-Meier plotter databases to study the prognostic correlation between ACE2 and various tumors. The correlation between ACE2 and immune infiltration levels was also investigated in TIMER database. We further explored the correlation between the ACE2 and the type markers of different immune cells in UCEC and KIRP.A prognosis analysis based on the expression levels of ACE2 of different tumors in ralated immune cells subgroup was further permormed. And the ACE2 promoter methylation profile was tested in the UALCAN database.In addition, we made use of the GSE30589 and GSE52920 databases to clarify changes in ACE2 expression in cells and animals following SARS-CoV infection. Results: ACE2 was elevated in both UCEC and KIRP, which suggests that tumor tissues are more likely to be infected with SARS-CoV-2 in UCEC and KIRP. High ACE2 had a favorable prognosis in UCEC and KIRP (OS HR0.47, 95%CI=0.30 to 0.73, OS HR0.44, 95%CI=0.24 to 0.81, respectively). In addition, the expression of ACE2 was positively correlated with the level of immune infiltration of macrophage (r=0.322, p<0.001) in KIRP. Similarly, ACE2 has a positive correlation with B cell (r=0.166, p<0.01), CD4+T cell (r=0.154, p<0.01), neutrophil (r=0.223, p<0.001) and dendritic cell (r=0.271, p<0.001) immune infiltration levels in UCEC. After correction of tumor purity, ACE2 in UCEC was significantly positively correlated with FCRL2 and MS4A1 in B cells, and FCGR3B, CEACAM3, SIGLEC5, CSF3R and S100A12 in neutrophils and CD84 in macrophages, while ACE2 in KIRP was positively correlated with CD68 and CD84 in macrophages. High ACE2 expression level has a favorable prognosis in the enriched B cells, CD4 + memory T cells, CD8 + T cells and macrophases subgroup in UCEC,and the enriched regulatory T cells and type 1 T helper cells subgroup in KIRP. Promoter methylation levels of ACE2 in UCEC and KIRP were significantly reduced, which explains to some extent the elevated ACE2 in UCEC and KIRP. Finally ,GSE30589 and GSE52920 databases were used to study the changes of ACE2 expression in vivo and in vitro, the results showed that ACE2 expression levels in both of them were reduced after SARS-CoV infection. Conclusions: ACE2 expression increased significantly in UCEC and KIRP. Elevated ACE2 was positively correlated with immune infiltration and prognosis of UCEC and KIRP. Moreover, tumor tissues are more susceptible to SARS-CoV-2 infection in COVID-19 patients with UCEC and KIRP.In the end, tumor tissues infected with SARS-CoV-2 maybe undergo a decrease in ACE2, and reduced ACE2 can brings about reduced immune infiltration in the tumor microenvironment, which may worsen the prognosis in UCEC and KIRP after SARS-CoV-2 infection. Funding Statement: This work was supported by grants from National Natural Science Foundation of China(81873486,81770327), Natural Scientific Fund of Jiangsu province (BK20161226), Jiangsu Province,s Key Provincial Talents Program (ZDRCA2016043), Jiangsu Province,s 333 High-Level Talents Project (BRA2017539), Jiangsu Provincial Medical Innovation Team (NO.CXTDA2017009). Declaration of Interest: The authors declare no conflicts of interest.