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CD47 Overexpression Is Associated with Epstein-Barr Virus Infection and Poor Prognosis in Patients with Nasopharyngeal Carcinoma.

ABSTRACT: Purpose: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. Materials and Methods: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. Results:In NPC patients, CD47 overexpression was significantly associated with disease recurrence (P=0.010), leading to poorer disease-free survival (DFS; P=0.002) and overall survival (P=0.021). Multivariate Cox proportional hazards models demonstrated that CD47 (HR=5.452, P=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. Conclusion:This study indicated that CD47 is related to EBV infection in NPC patients, and it is a feasible biomarker.

SUBMITTER: Wang ZH

PROVIDER: S-EPMC7183341 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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CD47 Overexpression Is Associated with Epstein-Barr Virus Infection and Poor Prognosis in Patients with Nasopharyngeal Carcinoma.

Wang Zhi-Hui ZH Pei Xiao-Feng XF Zhu Zhi-Quan ZQ Lin Zhong Z Mao Yin-Yan YY Xu Xiao-Lu XL Luo You-Li YL Zhang Li L Peng Pei-Jian PJ

OncoTargets and therapy 20200421

<h4>Purpose</h4>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.<h4>Materials and methods</h4>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 ...[more]

PMID: 32368091

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Project description:Nasopharyngeal carcinoma (NPC) is consistently associated with Epstein-Barr virus (EBV) infection in regions in which it is endemic, including Southern China and Southeast Asia. The high mortality rates of NPC patients with advanced and recurrent disease highlight the urgent need for effective treatments. While recent genomic studies have revealed few druggable targets, the unique interaction between the EBV infection and host cells in NPC strongly implies that targeting EBV may be an efficient approach to cure this virus-associated cancer. Key features of EBV-associated NPC are the persistence of an episomal EBV genome and the requirement for multiple viral latent gene products to enable malignant transformation. Many translational studies have been conducted to exploit these unique features to develop pharmaceutical agents and therapeutic strategies that target EBV latent proteins and induce lytic reactivation in NPC. In particular, inhibitors of the EBV latent protein EBNA1 have been intensively explored, because of this protein's essential roles in maintaining EBV latency and viral genome replication in NPC cells. In addition, recent advances in chemical bioengineering are driving the development of therapeutic agents targeting the critical functional regions of EBNA1. Promising therapeutic effects of the resulting EBNA1-specific inhibitors have been shown in EBV-positive NPC tumors. The efficacy of multiple classes of EBV lytic inducers for NPC cytolytic therapy has also been long investigated. However, the lytic-induction efficiency of these compounds varies among different EBV-positive NPC models in a cell-context-dependent manner. In each tumor, NPC cells can evolve and acquire somatic changes to maintain EBV latency during cancer progression. Unfortunately, the poor understanding of the cellular mechanisms regulating EBV latency-to-lytic switching in NPC cells limits the clinical application of EBV cytolytic treatment. In this review, we discuss the potential approaches for improvement of the above-mentioned EBV-targeting strategies.

Dataset Information

CD47 Overexpression Is Associated with Epstein-Barr Virus Infection and Poor Prognosis in Patients with Nasopharyngeal Carcinoma.

Publications

CD47 Overexpression Is Associated with Epstein-Barr Virus Infection and Poor Prognosis in Patients with Nasopharyngeal Carcinoma.

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