Caris Life Sciences, 4610 South 44th Place, Phoenix, AZ, 85040, USA.
Ruesch Center for the Cure of Gastrointestinal Cancers, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA.
Sci Rep. 2021 Mar 11;11(1):5639. doi: 10.1038/s41598-021-84731-7.
Patients with cancer demonstrate particularly poor outcomes from COVID-19. To provide information essential for understanding the biologic underpinnings of this association, we analyzed whole-transcriptome RNA expression data obtained from a large cohort of cancer patients to characterize expression of ACE2, TMPRSS2, and other proteases that are involved in viral attachment to and entry into target cells. We find substantial variability of expression of these factors across tumor types and identify subpopulations expressing ACE2 at very high levels. In some tumor types, especially in gastrointestinal cancers, expression of ACE2 and TMPRSS2 is highly correlated. Furthermore, we found infiltration with T-cell and natural killer (NK) cell infiltration to be particularly pronounced in ACE2-high tumors. These findings suggest that subsets of cancer patients exist with gene expression profiles that may be associated with heightened susceptibility to SARS-CoV-2 infection, in whom malignant tumors function as viral reservoir and possibly promote the frequently detrimental hyper-immune response in patients infected with this virus.
癌症患者在 COVID-19 中的预后尤其差。为了提供理解这种关联的生物学基础所必需的信息,我们分析了来自大量癌症患者的全转录组 RNA 表达数据,以表征 ACE2、TMPRSS2 和其他参与病毒附着和进入靶细胞的蛋白酶的表达。我们发现这些因素在肿瘤类型之间的表达存在很大的可变性,并确定了表达 ACE2 水平非常高的亚群。在某些肿瘤类型中,特别是在胃肠道癌症中,ACE2 和 TMPRSS2 的表达高度相关。此外,我们发现 ACE2 高表达的肿瘤中 T 细胞和自然杀伤 (NK) 细胞浸润特别明显。这些发现表明,存在具有可能与对 SARS-CoV-2 感染易感性增加相关的基因表达谱的癌症患者亚群,其中恶性肿瘤作为病毒库,并可能促进感染这种病毒的患者中经常出现的有害的过度免疫反应。