ACE2 Correlated With Immune Infiltration Serves as a Prognostic Biomarker in Endometrial Carcinoma and Renal Papillary Cell Carcinoma: Implication for COVID-19

Aging (Albany NY). 2020 Apr 27;12(8):6518-6535. doi: 10.18632/aging.103100. Epub 2020 Apr 27.

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.

Keywords: ACE2; COVID-19; SARS-CoV-2; immune infiltration.

MeSH terms

  • Betacoronavirus*
  • Biomarkers, Tumor
  • Carcinoma, Renal Cell* / immunology
  • Carcinoma, Renal Cell* / metabolism
  • Carcinoma, Renal Cell* / mortality
  • Coronavirus Infections* / immunology
  • Coronavirus Infections* / metabolism
  • Endometrial Neoplasms* / immunology
  • Endometrial Neoplasms* / metabolism
  • Endometrial Neoplasms* / mortality
  • Female
  • Humans
  • Immunity, Cellular*
  • Kidney Neoplasms* / immunology
  • Kidney Neoplasms* / metabolism
  • Kidney Neoplasms* / mortality
  • Pandemics*
  • Peptidyl-Dipeptidase A / biosynthesis*
  • Pneumonia, Viral* / immunology
  • Pneumonia, Viral* / metabolism
  • Prognosis

Substances

  • Biomarkers, Tumor
  • Peptidyl-Dipeptidase A
  • angiotensin converting enzyme 2

Supplementary concepts

  • COVID-19
  • severe acute respiratory syndrome coronavirus 2