Dan L. Duncan Comprehensive Cancer Center Division of Biostatistics, Baylor College of Medicine, Houston, TX, 77030, USA.
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, 77030, USA.
Sci Rep. 2021 Jan 28;11(1):2459. doi: 10.1038/s41598-021-82221-4.
A deeper understanding of the molecular biology of SARS-CoV-2 infection, including the host response to the virus, is urgently needed. Commonalities exist between the host immune response to viral infections and cancer. Here, we defined transcriptional signatures of SARS-CoV-2 infection involving hundreds of genes common across lung adenocarcinoma cell lines (A549, Calu-3) and normal human bronchial epithelial cells (NHBE), with additional signatures being specific to one or both adenocarcinoma lines. Cross-examining eight transcriptomic databases, we found that host transcriptional responses of lung adenocarcinoma cells to SARS-CoV-2 infection shared broad similarities with host responses to multiple viruses across different model systems and patient samples. Furthermore, these SARS-CoV-2 transcriptional signatures were manifested within specific subsets of human cancer, involving ~ 20% of cases across a wide range of histopathological types. These cancer subsets show immune cell infiltration and inflammation and involve pathways linked to the SARS-CoV-2 response, such as immune checkpoint, IL-6, type II interferon signaling, and NF-κB. The cell line data represented immune responses activated specifically within the cancer cells of the tumor. Common genes and pathways implicated as part of the viral host response point to therapeutic strategies that may apply to both SARS-CoV-2 and cancer.
深入了解 SARS-CoV-2 感染的分子生物学，包括宿主对病毒的反应，这是迫切需要的。宿主对病毒感染的免疫反应与癌症之间存在共同之处。在这里，我们定义了涉及数百个基因的 SARS-CoV-2 感染的转录特征，这些基因在肺腺癌细胞系（A549、Calu-3）和正常人类支气管上皮细胞（NHBE）中是常见的，而其他特征则是腺癌细胞系之一或两者所特有的。通过交叉检查八个转录组数据库，我们发现肺腺癌细胞对 SARS-CoV-2 感染的宿主转录反应与不同模型系统和患者样本中多种病毒的宿主反应具有广泛的相似性。此外，这些 SARS-CoV-2 转录特征表现在人类癌症的特定亚群中，涉及到多种组织病理学类型的约 20%的病例。这些癌症亚群表现出免疫细胞浸润和炎症，并涉及与 SARS-CoV-2 反应相关的途径，如免疫检查点、IL-6、II 型干扰素信号和 NF-κB。细胞系数据代表了肿瘤中癌细胞内特异性激活的免疫反应。作为病毒宿主反应的一部分而涉及的常见基因和途径表明，可能有针对 SARS-CoV-2 和癌症的治疗策略。
