ACE2 Correlated With Immune Infiltration Serves As A Novel Prognostic Biomarker In Clear Cell Renal Cell Carcinoma: Implication For COVID-19

Wuping Yang^1,2,3, Lei Li^1,2,3, Kenan Zhang^1,2,3, Kaifang Ma^1,2,3, Haibiao Xie^1,2,3, Yanqing Gong^1,2,3, Jingcheng Zhou^1,2,3✉, Kan Gong^1,2,3✉

1. Department of Urology, Peking University First Hospital, Beijing 100034, P.R. China
2. Hereditary Kidney Cancer Research Center, Peking University First Hospital, Beijing 100034, P.R. China
3. National Urological Cancer Center, Beijing 100034, P.R. China

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Citation:
Yang W, Li L, Zhang K, Ma K, Xie H, Gong Y, Zhou J, Gong K. ACE2 Correlated With Immune Infiltration Serves As A Novel Prognostic Biomarker In Clear Cell Renal Cell Carcinoma: Implication For COVID-19. Int J Biol Sci 2021; 17(1):20-31. doi:10.7150/ijbs.51969. Available from https://www.ijbs.com/v17p0020.htm

Abstract

The current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global infection, and is seriously threatening human life, especially cancer patients. Thus, we sought to determine the clinical roles of ACE2 (the cell entry receptor of SARS-CoV-2) in ccRCC (clear cell renal cell carcinoma). TCGA, GEO and TIP datasets, and immunohistochemistry and western blot results were used to determine the prognostic and clinicopathological characteristics of ACE2. ACE2 expression was down-regulated in ccRCC tissues and cell lines. The multivariate Cox regression analysis results indicated that increased ACE2 expression was independent predictor of longer OS (HR: 0.8259, 95%CI: 0.7734-0.8819, P<0.0001) and RFS (HR: 0.8023, 95%CI: 0.7375-0.8729, P<0.0001) in ccRCC patients. Lower ACE2 expression was also associated with advanced tumor stage, higher histological grade and pathological stage, and metastasis. Besides, ACE2 expression was significantly positively and negatively correlated with CD4 Naïve infiltration and CD4 Memory infiltration, respectively. Moreover, higher CD4 Naïve and lower CD4 Memory infiltration levels were associated with better pathological features and longer OS and RFS. Furthermore, high ACE2 expression group in decreased CD4 Naïve, enriched CD4 Naïve and enriched CD4 memory cohort had favorable prognosis. These findings identified that AEC2 was significantly reduced in ccRCC, and decreased ACE2 was related to worse pathological features and poor prognosis. Low ACE2 expression in ccRCC may partially affect the prognosis due to altered immune cells infiltration levels.

Keywords: COVID-19, ACE2, ccRCC, prognosis, immune infiltration