He Chaobin, Hua Xin, Sun Shuxin, Li Shaolong, Wang Jun, Huang Xin
Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, People's Republic of China.
Department of Experimental Research, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China.
J Inflamm Res. 2021 Mar 10;14:791-802. doi: 10.2147/JIR.S300127. eCollection 2021.
Cancer patients are more vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection than the general population, with lung epithelial cells or enterocytes being the main targets. However, the expressions of SARS-CoV-2 entry-related genes in aerodigestive cancers have not been fully elucidated.
In this study, the expressions of SARS-CoV-2 receptors and cofactors, including angiotensin I-converting enzyme 2 (ACE2), basigin (BSG) and transmembrane serine protease 2 (TMPRSS2), were comprehensively assessed. We compared BSG and TMPRSS2 expressions between aerodigestive cancers and matched normal tissues through Gene Expression Profiling Interactive Analysis 2 (GEPIA2). Furthermore, expressions in healthy colon tissues at different anatomical locations were explored using the Genotype-Tissue Expression (GTEx) dataset. In addition, expressions among different tumor stages and the prognostic values were detected through GEPIA2. Moreover, the correlation between gene expression and immune infiltration was explored via Tumor Immune Estimation Resource (TIMER). Finally, expressions in primary colorectal cancer (CRC), lung metastasis and liver metastasis were investigated using the Gene Expression Omnibus (GEO) dataset GSE41258.
Similar to ACE2, TMPRSS2 and BSG were also highly expressed in the digestive tracts. Intriguingly, BSG/TMPRSS2 expression in adjacent normal colon tissue or lung tissue was higher than that in corresponding healthy tissue, whereas they varied not among different tumor stages and correlated not with prognosis in aerodigestive cancers. Moreover, ACE2 was expressed at higher levels in lung metastases from CRC than in normal lung tissues.
SARS-CoV-2 entry genes were highly expressed in CRC, and we reported for the first time higher expression of ACE2 in lung metastases from CRC than in normal lung, indicating that these patients may be more susceptible to extrapulmonary or pulmonary SARS-CoV-2 infection. Since our study is a bioinformatic analysis, further experimental evidences and clinical data are urgently needed.
癌症患者比普通人群更容易感染严重急性呼吸综合征冠状病毒2（SARS-CoV-2），肺上皮细胞或肠上皮细胞是主要靶标。然而，SARS-CoV-2进入相关基因在气消化道癌症中的表达尚未完全阐明。
在本研究中，全面评估了SARS-CoV-2受体和辅助因子的表达，包括血管紧张素I转换酶2（ACE2）、基底膜蛋白（BSG）和跨膜丝氨酸蛋白酶2（TMPRSS2）。我们通过基因表达谱交互分析2（GEPIA2）比较了气消化道癌症与匹配的正常组织之间的BSG和TMPRSS2表达。此外，使用基因型-组织表达（GTEx）数据集探索了不同解剖位置的健康结肠组织中的表达。此外，通过GEPIA2检测不同肿瘤阶段的表达及其预后价值。此外，通过肿瘤免疫估计资源（TIMER）探索基因表达与免疫浸润之间的相关性。最后，使用基因表达综合数据库（GEO）数据集GSE41258研究原发性结直肠癌（CRC）、肺转移和肝转移中的表达。
与ACE2类似，TMPRSS2和BSG在消化道中也高表达。有趣的是，相邻正常结肠组织或肺组织中的BSG/TMPRSS2表达高于相应的健康组织，而它们在不同肿瘤阶段之间没有差异，并且与气消化道癌症的预后无关。此外，CRC肺转移中ACE2的表达水平高于正常肺组织。
SARS-CoV-2进入基因在CRC中高表达，我们首次报道CRC肺转移中ACE2的表达高于正常肺组织，表明这些患者可能更容易发生肺外或肺部SARS-CoV-2感染。由于我们的研究是一项生物信息学分析，迫切需要进一步的实验证据和临床数据。
