Wang Zhi-Hui, Pei Xiao-Feng, Zhu Zhi-Quan, Lin Zhong, Mao Yin-Yan, Xu Xiao-Lu, Luo You-Li, Zhang Li, Peng Pei-Jian
State Key Laboratory of Oncology in South China, Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China.
Department of Thoracic Oncology, The Cancer Center of the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, People's Republic of China.
Onco Targets Ther. 2020 Apr 21;13:3325-3334. doi: 10.2147/OTT.S245023. eCollection 2020.
Little is known about the clinical significance of CD47 expression and its association with Epstein-Barr virus (EBV) infection in patients with nasopharyngeal carcinoma (NPC). The aim of this study was to clarify the prognostic value and role of CD47 in EBV-associated NPC.
Sixty-six cases of non-metastatic NPC were retrospectively reviewed. Tissues were collected for immunohistochemical staining of CD47 and the EBV-encoded oncoprotein latent membrane protein 1 (LMP1). Western blotting and quantitative real-time PCR were performed to determine the CD47 and LMP1 levels in common human NPC cell lines. Additionally, CD47 and LMP1 expression in a constructed EBV-positive human NPC cell (CNE-2-EBV+) and a stable cell line transfected with LMP1 plasmid (CNE-2-LMP1) was assessed. Next, we used Western blotting to assess the decrease in CD47 expression on CNE-2-LMP1 cells after transfecting them with small interfering RNA (siRNA)-targeting LMP1.
In NPC patients, CD47 overexpression was significantly associated with disease recurrence (=0.010), leading to poorer disease-free survival (DFS; =0.002) and overall survival (=0.021). Multivariate Cox proportional hazards models demonstrated that CD47 (HR=5.452, =0.016) was an independent prognostic factor of DFS. Moreover, CD47 expression was associated with plasma EBV-DNA copy number and LMP1 tissue expression. Among the human NPC cell lines, CD47 and LMP1 expression was notably higher in the EBV-positive C666-1 cell line than in the EBV-negative cell lines. Furthermore, EBV infection upregulated CD47 expression via LMP1-mediated pathways in human NPC cells.
This study indicated that CD47 is related to EBV infection in NPC patients, and it is a feasible biomarker.
对于鼻咽癌（NPC）患者中CD47表达的临床意义及其与爱泼斯坦-巴尔病毒（EBV）感染的关联知之甚少。本研究的目的是阐明CD47在EBV相关鼻咽癌中的预后价值和作用。
回顾性分析66例非转移性鼻咽癌病例。收集组织进行CD47和EBV编码的癌蛋白潜伏膜蛋白1（LMP1）的免疫组化染色。进行蛋白质免疫印迹法和定量实时聚合酶链反应以测定常见人类鼻咽癌细胞系中CD47和LMP1的水平。此外，评估构建的EBV阳性人类鼻咽癌细胞（CNE-2-EBV+）和用LMP1质粒转染的稳定细胞系（CNE-2-LMP1）中CD47和LMP1的表达。接下来，我们用蛋白质免疫印迹法评估用靶向LMP1的小干扰RNA（siRNA）转染CNE-2-LMP1细胞后CD47表达的降低情况。
在鼻咽癌患者中，CD47过表达与疾病复发显著相关（P=0.010），导致无病生存期（DFS；P=0.002）和总生存期（P=0.021）较差。多变量Cox比例风险模型表明CD47（HR=5.452，P=0.016）是DFS的独立预后因素。此外，CD47表达与血浆EBV-DNA拷贝数和LMP1组织表达相关。在人类鼻咽癌细胞系中，EBV阳性的C666-1细胞系中CD47和LMP1的表达明显高于EBV阴性细胞系。此外，EBV感染通过LMP1介导的途径上调人类鼻咽癌细胞中CD47的表达。
本研究表明CD47与鼻咽癌患者的EBV感染相关，并且它是一种可行的生物标志物。
