The inhibitory effect of ACE2 expression on human tumor proliferation in ccRCC was further confirmed by in vitro and in preclinical animal models showing that lower ACE2 expression was also associated with advanced tumor stage (T3/T4), higher histological grade (grade 3/4), pathological stage (III/IV) and metastasis (M1) [47,48]. This evidence concerns the gene ACE2 and nonpapillary renal cell carcinoma.