Table_9_The Potential Mechanism of Cancer Patients Appearing More Vulnerable to SARS-CoV-2 and Poor Outcomes: A Pan-Cancer Bioinformatics Analysis.xls

To explore the potential mechanism of cancer patients appearing more vulnerable to SARS-CoV-2 infection and poor COVID-19 outcomes, we conducted an integrative bioinformatics analysis for SARS-CoV-2-required genes and host genes and variants related to SARS-CoV-2 susceptibility and COVID-19 severity. BLCA, HNSC, KIRC, KIRP, LGG, PCPG, PRAD, TGCT, and THCA patients carrying rs10774671-A (OAS1) genotype may be more likely to have poor COVID-19 outcomes relative to those who carry rs10774671-G, because individuals carrying rs10774671-A will have lower expression of OAS1, which serves as a protective factor against SARS-CoV-2 processes and poor COVID-19 outcomes. SARS-CoV-2-required genes were correlated with TME, immune infiltration, overall survival, and anti-cancer drug sensitivity. CHOL patients may have a higher risk of SARS-CoV-2 infection than healthy subjects. SARS-CoV-2-induced ACE2 and NPC1 elevation may have a negative influence on the immune responses of LUSC and CD8+T infiltration of LUAD, and negatively affect the sensitivity of anti-lung cancer drugs. LUSC and LUAD patients may have a varying degree of adverse outcomes if they are infected with SARS-CoV-2. miR-760 may target and inhibit ACE2 expression. Cancer patients appearing vulnerable to SARS-CoV-2 infection and having poor COVID-19 outcomes may be partly due to host genetic factors and dysregulation of SARS-CoV-2-required genes. OAS1, ACE2, and miR-760 could serve as the treatment and intervention targets for SARS-CoV-2.

为探索癌症患者更易感染严重急性呼吸综合征冠状病毒2（SARS-CoV-2）且新型冠状病毒肺炎（COVID-19）预后较差的潜在机制，本研究针对新冠病毒必需基因、与SARS-CoV-2易感性及COVID-19重症程度相关的宿主基因和变异开展了整合生物信息学分析。携带rs10774671-A（寡腺苷酸合成酶1，OAS1）基因型的BLCA、HNSC、KIRC、KIRP、LGG、PCPG、PRAD、TGCT及THCA患者，相较于携带rs10774671-G基因型的患者，更易出现不良的COVID-19预后，原因在于携带rs10774671-A的个体其OAS1表达水平更低，而OAS1是对抗SARS-CoV-2感染进程及不良COVID-19预后的保护性因子。SARS-CoV-2必需基因与肿瘤微环境（Tumor Microenvironment, TME）、免疫浸润、总生存期及抗癌药物敏感性显著相关。CHOL患者感染SARS-CoV-2的风险可能高于健康受试者。SARS-CoV-2诱导的血管紧张素转换酶2（ACE2）及尼曼匹克C1蛋白（NPC1）表达上调，可对肺鳞状细胞癌（LUSC）的免疫应答及肺腺癌（LUAD）的CD8+T细胞浸润产生负向影响，同时会降低抗肺癌药物的敏感性。若感染SARS-CoV-2，LUSC及LUAD患者可能出现不同程度的不良预后。微RNA-760（miR-760）可靶向抑制ACE2的表达。癌症患者更易感染SARS-CoV-2且COVID-19预后较差的现象，可能部分源于宿主遗传因素及SARS-CoV-2必需基因的表达失调。寡腺苷酸合成酶1（OAS1）、血管紧张素转换酶2（ACE2）及微RNA-760（miR-760）可作为SARS-CoV-2感染的治疗及干预靶点。