OncoTargets and Therapy (Dec 2018)
Upregulation of valosin-containing protein (VCP) is associated with poor prognosis and promotes tumor progression of orbital B-cell lymphoma
Abstract
Wenwen Zhu,1 Di Li,2,3 Lihua Xiao4 1Department of Ophthalmology, Affiliated Hospital of Weifang Medical College, Weifang, Shandong, China; 2Institute of Rehabilitation Medicine of China, China Rehabilitation Science Institute, China Rehabilitation Research Center, Beijing, China; 3Beijing Key Laboratory of Neural Injury and Rehabilitation, Beijing, China; 4Institute of Orbital Disease, General Hospital of Chinese People’s Armed Police Forces, Beijing, China Objective: This 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. Methods: We 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. Results: Expression 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. Downregulation of VCP with siRNA did not inhibit cell proliferation. However, it dramatically increased apoptosis and suppressed the invasion of B-cell lymphoma cells. Conclusion: VCP 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. Keywords: VCP, orbital B-cell lymphoma, prognosis, invasion, apoptosis
