Zhang Zhilan, Li Lin, Li Mengyuan, Wang Xiaosheng
Biomedical Informatics Research Lab, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, China.
Cancer Genomics Research Center, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, China.
Comput Struct Biotechnol J. 2020;18:2438-2444. doi: 10.1016/j.csbj.2020.08.024. Epub 2020 Sep 2.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 29 million people and has caused more than 900,000 deaths worldwide as of September 14, 2020. The SARS-CoV-2 human cell receptor ACE2 has recently received extensive attention for its role in SARS-CoV-2 infection Many studies have also explored the association between ACE2 and cancer. However, a systemic investigation into associations between ACE2 and oncogenic pathways, tumor progression, and clinical outcomes in pan-cancer remains lacking. Using cancer genomics datasets from the Cancer Genome Atlas (TCGA) program, we performed computational analyses of associations between expression and antitumor immunity, immunotherapy response, oncogenic pathways, tumor progression phenotypes, and clinical outcomes in 13 cancer cohorts. We found that upregulation was associated with increased antitumor immune signatures and expression, and favorable anti-PD-1/PD-L1/CTLA-4 immunotherapy response. expression levels inversely correlated with the activity of cell cycle, mismatch repair, TGF-β, Wnt, VEGF, and Notch signaling pathways. Moreover, expression levels had significant inverse correlations with tumor proliferation, stemness, and epithelial-mesenchymal transition. upregulation was associated with favorable survival in pan-cancer and in multiple individual cancer types. These results suggest that ACE2 is a potential protective factor for cancer progression. Our data may provide potential clinical implications for treating cancer patients infected with SARS-CoV-2.
截至2020年9月14日，严重急性呼吸综合征冠状病毒2（SARS-CoV-2）已感染全球超过2900万人，并导致超过90万人死亡。SARS-CoV-2的人类细胞受体血管紧张素转换酶2（ACE2）因其在SARS-CoV-2感染中的作用最近受到广泛关注。许多研究也探讨了ACE2与癌症之间的关联。然而，目前仍缺乏对ACE2与泛癌中致癌途径、肿瘤进展及临床结局之间关联的系统性研究。利用来自癌症基因组图谱（TCGA）项目的癌症基因组数据集，我们对13个癌症队列中ACE2表达与抗肿瘤免疫、免疫治疗反应、致癌途径、肿瘤进展表型及临床结局之间的关联进行了计算分析。我们发现ACE2上调与抗肿瘤免疫特征增加、免疫相关基因表达及抗程序性死亡蛋白1（PD-1）/程序性死亡配体1（PD-L1）/细胞毒性T淋巴细胞相关抗原4（CTLA-4）免疫治疗反应良好有关。ACE2表达水平与细胞周期、错配修复、转化生长因子-β（TGF-β）、Wnt、血管内皮生长因子（VEGF）和Notch信号通路的活性呈负相关。此外，ACE2表达水平与肿瘤增殖、干性及上皮-间质转化呈显著负相关。ACE2上调与泛癌及多种个体癌症类型的良好生存相关。这些结果表明ACE2是癌症进展的潜在保护因子。我们的数据可能为治疗感染SARS-CoV-2的癌症患者提供潜在的临床启示。
