Key Laboratory of Epigenetics and Oncology, Research Center for Preclinical Medicine, Southwest Medical University, Luzhou, China.
Department of Pathology, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huai'an, China.
Front Immunol. 2022 Jun 3;13:923516. doi: 10.3389/fimmu.2022.923516. eCollection 2022.
SARS-Cov-2 caused the COVID-19 pandemic worldwide. ADAM17 functions as a disintegrin and transmembrane metalloproteinase domain protein involved in the regulation of SARS-CoV-2 receptor ACE2. However, its impact on cancer patients infected with COVID-19 and its correlation with immune cell infiltration is unclear. This study compared ADAM17 expression between normal and tumor tissues based on GEPIA. The correlations between ADAM17 expression and immune cell infiltration and immunomodulators were investigated. Besides, treated drugs for targeting ADAM17 were searched in the TISDB database. We found that ADAM17 was highly conserved in many species and was mainly expressed in lung, brain, female tissues, bone marrow and lymphoid tissues. It was also highly expressed in respiratory epithelial cells of rhinitis and bronchus. ADAM17 expression in tumors was higher than that in several paired normal tissues and was negatively correlated with the prognosis of patients with malignant tumors. Interestingly, ADAM17 expression significantly correlated with immunomodulators and immune cell infiltration in normal and tumor tissues. Moreover, eight small molecules targeting ADAM17 only demonstrate therapeutic significance. These findings imply important implications for ADAM17 in cancer patients infected with COVID-19 and provide new clues for development strategy of anti-COVID-19.
SARS-CoV-2 导致了全球范围内的 COVID-19 大流行。ADAM17 是一种解整合素和跨膜金属蛋白酶结构域蛋白,参与 SARS-CoV-2 受体 ACE2 的调节。然而,其对感染 COVID-19 的癌症患者的影响及其与免疫细胞浸润的相关性尚不清楚。本研究基于 GEPIA 比较了正常组织和肿瘤组织中的 ADAM17 表达。研究了 ADAM17 表达与免疫细胞浸润和免疫调节剂之间的相关性。此外,还在 TISDB 数据库中搜索了针对 ADAM17 的治疗药物。我们发现 ADAM17 在许多物种中高度保守,主要在肺、脑、女性组织、骨髓和淋巴组织中表达。它在鼻炎和支气管的呼吸道上皮细胞中也高度表达。肿瘤中的 ADAM17 表达高于几种配对的正常组织,并且与恶性肿瘤患者的预后呈负相关。有趣的是,ADAM17 在正常和肿瘤组织中的表达与免疫调节剂和免疫细胞浸润显著相关。此外,只有 8 种针对 ADAM17 的小分子显示出治疗意义。这些发现提示 ADAM17 在感染 COVID-19 的癌症患者中具有重要意义,并为抗 COVID-19 的开发策略提供了新线索。