ACE2 correlated with immune infiltration serves as a prognostic biomarker in endometrial carcinoma and renal papillary cell carcinoma: implication for COVID-19

Abstract

Angiotensin-converting enzyme 2 (ACE2) is a member of the renin-angiotension system, however, the correlation between ACE2 and prognosis in UCEC (Uterine Corpus Endometrial Carcinoma) and KIRP (Kidney Renal Papillary Cell Carcinoma) is not clear. We analyzed the expression levels of ACE2 in the Oncomine and TIMER databases, the correlation between ACE2 and overall survival in the PrognoScan, GEPIA and Kaplan-Meier plotter databases. The correlation between ACE2 and immune infiltration level and the type markers of immune cells was investigated in TIMER database. A prognosis analysis based on the expression levels of ACE2 was further performed in related immune cells subgroup. The ACE2 promoter methylation profile was tested in the UALCAN database. In addition, we used GSE30589 and GSE52920 databases to elucidate the changes of ACE2 expression in vivo and in vitro after SARS-CoV infection. ACE2 was elevated in UCEC and KIRP, and high ACE2 had a favorable prognosis. The expression of ACE2 was positively correlated with the level of immune infiltration of macrophage in KIRP, B cell, CD4+T cell, neutrophil and dendritic cell immune infiltration levels in UCEC. ACE2 was significantly positively correlated with the type markers of B cells and neutrophils, macrophages in UCEC, while ACE2 in KIRP was positively correlated with the type markers of macrophages. High ACE2 expression level had a favorable prognosis in different enriched immune cells subgroups in UCEC and KIRP. And the promoter methylation levels of ACE2 in UCEC and KIRP were significantly reduced. What's more, we found that the expression of ACE2 decreased in vivo and in vitro after SARS-CoV infection. In conclusion, ACE2 expression increased significantly in UCEC and KIRP, elevated ACE2 was positively correlated with immune infiltration and prognosis. Moreover, tumor tissues may be more susceptible to SARS-CoV-2 infection in COVID-19 patients with UCEC and KIRP, which may worsen the prognosis.

Pan-Cancer Analysis Reveals that the SARS-CoV-2 Receptor ACE2 is a Protective Factor for Cancer Progression

“…In particular, the ACE2 downregulation correlates with worse survival and tumor advancement in KIRC, also known as clear cell renal cell carcinoma (ccRCC). Previous studies demonstrated that ACE2 exerts antitumor effects by inhibiting tumor angiogenesis [10] and promoting tumor immune in ltration [14]. Our results are consistent with these previous ndings.…”

“…Moreover, ACE2 de ciency may exacerbate outcomes in patients with SARS-CoV-2 infection [27]. Indeed, a recent study showed that ACE2 was downregulated in virus-infected lung tissue [14], indicating a potential protective role of ACE2 in patients with SARS-CoV-2 infection. Thus, using ACE2 inhibitors for preventing and treating SARS-CoV-2 infections may not be an advisable strategy for individuals with hypertension, heart disease, or cancers.…”

“…Several studies demonstrated that ACE2 had antitumor effects by inhibiting tumor angiogenesis [10,11,13]. A recent study [14] showed that ACE2 expression was associated with increased tumor immune in ltration and was a positive prognostic factor in uterine corpus endometrial and renal papillary cell cancers. Nevertheless, a systemic investigation into the association between ACE2 expression and antitumor immunity, oncogenic pathways, tumor progression phenotypes, and clinical outcomes in pan-cancer remains lacking.…”

Does Endometriosis Increase Susceptibility to COVID–19 Infections? A case-control study in Women of Reproductive Age

“…However, the susceptibility of endometrial tissue to COVID-19 has not been con rmed in the clinical setting (14). Studying large databases has shown that the uterine corpus endometrial carcinoma tissue is more susceptible to SARS-CoV-2 infection, which also affected the tumor prognosis after COVID-19 infection (27). Other cancer types, including gastrointestinal and urinary tract tumors have also shown higher susceptibility to COVID-19 infection, attributed to the expression of ACE 2 and TMPRSS2 in cancer tissues (22,28).…”

Three-gene prognostic biomarkers for seminoma identified by weighted gene co-expression network analysis

“…Subsequently, correlations between prognostic biomarker expression and gene markers of tumor-infiltrating immune cells were further explored using Spearman’s correlation. Gene markers have been reported in previous studies [ 20 ].…”