Department of Urology, Peking University First Hospital, Beijing 100034, P.R. China.
Hereditary Kidney Cancer Research Center, Peking University First Hospital, Beijing 100034, P.R. China.
Int J Biol Sci. 2021 Jan 1;17(1):20-31. doi: 10.7150/ijbs.51969. eCollection 2021.
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.
目前严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）已在全球范围内引发感染，严重威胁着人类生命，尤其是癌症患者。因此，我们试图确定 ACE2（SARS-CoV-2 的细胞进入受体）在 ccRCC（透明细胞肾细胞癌）中的临床作用。我们使用 TCGA、GEO 和 TIP 数据集以及免疫组织化学和 Western blot 结果来确定 ACE2 的预后和临床病理特征。ACE2 在 ccRCC 组织和细胞系中表达下调。多变量 Cox 回归分析结果表明，ACE2 表达增加是 ccRCC 患者 OS（HR：0.8259，95%CI：0.7734-0.8819，P<0.0001）和 RFS（HR：0.8023，95%CI：0.7375-0.8729，P<0.0001）更长的独立预测因子。ACE2 表达降低与肿瘤分期较晚、组织学分级和病理分期较高以及转移有关。此外，ACE2 表达与 CD4 Naive 浸润和 CD4 记忆浸润分别呈显著正相关和负相关。此外，CD4 Naive 浸润水平较高和 CD4 记忆浸润水平较低与较好的病理特征和较长的 OS 和 RFS 相关。此外，在降低 CD4 Naive、富集 CD4 Naive 和富集 CD4 记忆队列中，高 ACE2 表达组具有良好的预后。这些发现表明 ACE2 在 ccRCC 中显著减少，而减少的 ACE2 与较差的病理特征和不良预后有关。ccRCC 中 ACE2 表达降低可能部分由于免疫细胞浸润水平改变而影响预后。
