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      Effect of latent membrane protein 1 expression on overall survival in Epstein-Barr virus-associated cancers: a literature-based meta-analysis

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          Abstract

          Latent membrane protein 1 (LMP1) is identified as the main transforming oncoprotein of Epstein-Barr virus (EBV). LMP1 is frequently expressed in a variety of EBV-associated cancers, including nasopharyngeal carcinoma (NPC), non-Hodgkin lymphoma (NHL), Hodgkin disease (HD), and gastric cancer (GC). However, due to conflicting results, the prognostic value of LMP1 expression on clinical outcomes in EBV-associated cancers remains unclear. We performed a meta-analysis on 32 studies with a total of 3752 patients to explore the association between LMP1 expression and overall survival (OS) in EBV-associated cancers. Overall, LMP1 expression was significantly associated with poorer OS (hazard ratio, HR = 1.51, 95% confidence interval, CI, 1.13–2.03), irrespective of cancer type. Further analyses showed that LMP1 expression correlated with poorer OS in NPC (HR = 2.48, 95% CI, 1.77–3.47) and NHL patients (HR = 1.83, 95% CI, 1.07–3.15), but not in HD patients (HR = 0.98, 95% CI, 0.60–1.62) or GC patients (HR = 0.70, 95% CI, 0.44–1.12). Subgroup analyses indicated that the age and geographical factors seemed to have an effect on the clinical outcomes of HD patients with positive LMP1 expression. In conclusion, LMP1 expression can be used as a prognostic biomarker in NPC, NHL, and certain HD patients. This data suggests that novel therapies targeting LMP1 may improve clinical outcomes for EBV-associated cancer patients.

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          Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints.

          Meta-analyses aim to provide a full and comprehensive summary of related studies which have addressed a similar question. When the studies involve time to event (survival-type) data the most appropriate statistics to use are the log hazard ratio and its variance. However, these are not always explicitly presented for each study. In this paper a number of methods of extracting estimates of these statistics in a variety of situations are presented. Use of these methods should improve the efficiency and reliability of meta-analyses of the published literature with survival-type endpoints.
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            The role of the EBV-encoded latent membrane proteins LMP1 and LMP2 in the pathogenesis of nasopharyngeal carcinoma (NPC).

            Although frequently expressed in EBV-positive malignancies, the contribution of the oncogenic latent membrane proteins, LMP1 and LMP2, to the pathogenesis of nasopharyngeal carcinoma (NPC) is not fully defined. As a key effector in EBV-driven B cell transformation and an established "transforming" gene, LMP1 displays oncogenic properties in rodent fibroblasts and induces profound morphological and phenotypic effects in epithelial cells. LMP1 functions as a viral mimic of the TNFR family member, CD40, engaging a number of signalling pathways that induce morphological and phenotypic alterations in epithelial cells. Although LMP2A plays an essential role in maintaining viral latency in EBV infected B cells, its role in epithelial cells is less clear. Unlike LMP1, LMP2A does not display "classical" transforming functions in rodent fibroblasts but its ability to engage a number of potentially oncogenic cell signalling pathways suggests that LMP2A can also participate in EBV-induced epithelial cell growth transformation. Here we review the effects of LMP1 and LMP2 on various aspects of epithelial cell behaviour highlighting key aspects that may contribute to the pathogenesis of NPC. Copyright © 2012 Elsevier Ltd. All rights reserved.
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              Clinicopathological and molecular characteristics of Epstein-Barr virus-associated gastric carcinoma: a meta-analysis.

              There is conflicting data regarding the clinicopathological significance of the risk factors associated with Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC). To address this controversy, we performed a meta-analysis for the clinicopathological and molecular characteristics of EBVaGC. The relevant published studies were reviewed according to the defined selection criteria. The effect sizes of the outcome parameters were estimated by an odds ratio or a weighted mean difference. This meta-analysis included 48 studies that encompassed a total of 9738 patients. The frequency of EBVaGC was 8.8%, and EBVaGC was significantly associated with ethnicity. It was more predominant in men and in younger individuals. Interestingly, EBVaGC was more prevalent in Caucasian and Hispanic patients than in Asian ones. EBVaGC developed most often in the cardia and body, and it generally showed the diffuse histological type. EBV was highly prevalent in the patients with lymphoepithelial carcinoma. EBVaGC was closely associated with remnant cancer and a CpG island methylator-high status, but not with Helicobacter pylori infection, a TP53 expression, and p53 mutation. In addition, EBVaGC was not significantly associated with the depth of invasion, lymph node metastasis, or the clinical stage. The clinicopathological and molecular characteristics of EBVaGC are quite different from those of conventional gastric adenocarcinoma. However, further study is needed to determine the effect of EBV on the survival of EBVaGC patients.
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                Author and article information

                Journal
                Oncotarget
                Oncotarget
                ImpactJ
                Oncotarget
                Impact Journals LLC
                1949-2553
                6 October 2015
                18 August 2015
                : 6
                : 30
                : 29311-29323
                Affiliations
                1 Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China
                Author notes
                Article
                10.18632/oncotarget.4906
                4745728
                26336130
                1e8998b7-4fe3-468b-9ebe-c46c420fa6c1
                Copyright: © 2015 Chen et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 20 May 2015
                : 7 August 2015
                Categories
                Research Paper

                Oncology & Radiotherapy
                lmp1,ebv,cancer,survival,meta-analysis
                Oncology & Radiotherapy
                lmp1, ebv, cancer, survival, meta-analysis

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