Upregulation of valosin-containing protein (VCP) is associated with poor prognosis and promotes tumor progression of orbital B-cell lymphoma.

Abstract

ObjectiveThis study aimed to investigate the relationship between VCP expression and the prognosis of orbital B-cell lymphoma patients and the influence of downregulation of VCP on the apoptosis and invasion abilities of lymphoma cells.MethodsWe recruited 66 orbital B-cell lymphoma patients. VCP expression in 66 samples of orbital B-cell lymphoma was determined by immunohistochemistry using monoclonal VCP antibodies. Based on VCP-expression levels detected by immunohistochemistry, we chose ten cases of orbital tumor paraffin tissue from the patients. Total RNA was extracted and differences in VCP gene-expression levels compared among patients using quantitative reverse-transcription (qRT) PCR. We used siRNA to knock down VCP in the lymphoma cell lines Raji and SUDHL4. qRT-PCR and Western blot were applied to detect VCP mRNA and protein expression, respectively. SUDHL48 assays were applied to investigate cell proliferation. Hoechst 33258 staining and flow-cytometry analysis were applied to investigate cell apoptosis. Transwell assays were applied to investigate invasive ability. Survival analysis was used to evaluate prognostic values.ResultsExpression levels of VCP were correlated with the stage, tumor grade, and recurrence rate of patients. VCP mRNA-expression levels were consistent with VCP-expression levels in orbital B-cell lymphoma tissue. Moreover, survival analysis revealed that lower VCP-expression levels were correlated with longer overall survival of orbital B-cell lymphoma patients. Down-regulation of VCP with siRNA did not inhibit cell proliferation. However, it dramatically increased apoptosis and suppressed the invasion of B-cell lymphoma cells.ConclusionVCP expression played an important role in the progression of orbital B-cell lymphoma. VCP could be a useful marker for predicting the prognosis of orbital B-cell lymphoma patients. VCP may be a potential therapeutic target for orbital B-cell lymphoma.