An Xiang, Lin Wenlong, Liu Huan, Zhong Weixiang, Zhang Xiuming, Zhu Yimin, Wang Xiaojian, Li Jun, Sheng Qinsong
Institute of Immunology and Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Department of Pathology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Front Cell Dev Biol. 2021 Jun 11;9:659809. doi: 10.3389/fcell.2021.659809. eCollection 2021.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells through interactions with its receptor, Angiotensin-converting enzyme 2 (ACE2), causing severe acute respiratory syndrome and death in a considerable proportion of people. Patients infected with SARS-CoV-2 experience digestive symptoms. However, the precise protein expression atlas of ACE2 in the gastrointestinal tract remains unclear. In this study, we aimed to explore the ACE2 protein expression pattern and the underlying function of ACE2 in the gastrointestinal tract, including the colon, stomach, liver, and pancreas.
We measured the protein expression of ACE2 in the gastrointestinal tract using immunohistochemical (IHC) staining with an ACE2-specific antibody of paraffin-embedded colon, stomach, liver, and pancreatic tissues. The correlation between the protein expression of ACE2 and the prognosis of patients with gastrointestinal cancers was analyzed by the log-rank (Mantel-Cox) test. The influence of ACE2 on colon, stomach, liver, and pancreatic tumor cell line proliferation was tested using a Cell Counting Kit 8 (CCK-8) assay.
ACE2 presented heterogeneous expression patterns in the gastrointestinal tract, and it showed a punctate distribution in hepatic cells. Compared to that in parallel adjacent non-tumor tissues, the protein expression of ACE2 was significantly increased in colon cancer, stomach cancer, and pancreatic cancer tissues but dramatically decreased in liver cancer tissues. However, the expression level of the ACE2 protein was not correlated with the survival of patients with gastrointestinal cancers. Consistently, ACE2 did not affect the proliferation of gastrointestinal cancer cells .
The ACE2 protein is widely expressed in the gastrointestinal tract, and its expression is significantly altered in gastrointestinal tumor tissues. ACE2 is not an independent prognostic marker of gastrointestinal cancers.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）通过与其受体血管紧张素转换酶2（ACE2）相互作用感染宿主细胞，在相当一部分人中导致严重急性呼吸综合征和死亡。感染SARS-CoV-2的患者会出现消化系统症状。然而，胃肠道中ACE2精确的蛋白质表达图谱仍不清楚。在本研究中，我们旨在探索ACE2在胃肠道（包括结肠、胃、肝脏和胰腺）中的蛋白质表达模式及其潜在功能。
我们使用针对石蜡包埋的结肠、胃、肝脏和胰腺组织的ACE2特异性抗体进行免疫组织化学（IHC）染色，测量胃肠道中ACE2的蛋白质表达。通过对数秩（Mantel-Cox）检验分析ACE2蛋白质表达与胃肠道癌症患者预后之间的相关性。使用细胞计数试剂盒8（CCK-8）检测ACE2对结肠、胃、肝脏和胰腺肿瘤细胞系增殖的影响。
ACE2在胃肠道呈现异质性表达模式，在肝细胞中呈点状分布。与平行相邻的非肿瘤组织相比，ACE2在结肠癌、胃癌和胰腺癌组织中的蛋白质表达显著增加，而在肝癌组织中显著降低。然而，ACE2蛋白质的表达水平与胃肠道癌症患者的生存率无关。一致地，ACE2不影响胃肠道癌细胞的增殖。
ACE2蛋白在胃肠道广泛表达，其表达在胃肠道肿瘤组织中显著改变。ACE2不是胃肠道癌症的独立预后标志物。
