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.
Highlights
Epstein-Barr virus (EBV) is a ubiquitous tumorigenic human herpes virus carried in more than 90% of adult populations worldwide [1]
Further analyses showed that Latent membrane protein 1 (LMP1) expression correlated with poorer overall survival (OS) in nasopharyngeal carcinoma (NPC) (HR = 2.48, 95% confidence interval (CI), 1.77–3.47) and non-Hodgkin lymphoma (NHL) patients (HR = 1.83, 95% CI, 1.07–3.15), but not in Hodgkin disease (HD) patients (HR = 0.98, 95% CI, 0.60–1.62) or gastric cancer (GC) patients (HR = 0.70, 95% CI, 0.44–1.12)
We conducted a meta-analysis of 3752 patients included in 32 studies, and found that EBV-associated cancer patients with positive expression of LMP1 had significantly poorer survival than those with negative expression
Summary
Epstein-Barr virus (EBV) is a ubiquitous tumorigenic human herpes virus carried in more than 90% of adult populations worldwide [1]. LMP1 is an integral membrane protein comprising three domains: a short cytoplasmic N-terminus, six transmembrane spanning regions, and a large cytoplasmic C-terminal tail [4] It activates the tumor necrosis factor receptor (TNFR) signaling pathway through recruitment of TNFR-associated factors and other adaptor proteins, and stimulates or inhibits several other signaling pathways, including NF-kB and PI3-K/Akt [3, 4]. Through these signaling events, LMP1 has been shown to transform rodent fibroblast cells, cause B lymphocyte immortalization in vitro, and induce hyperplasia in transgenic mice [5]. LMP1 is attracting considerable attention as a potential prognostic biomarker and novel therapeutic target
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