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含缬酪肽蛋白（VCP）的上调与预后不良相关，并促进眼眶B细胞淋巴瘤的肿瘤进展。

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

作者信息

Zhu Wenwen, Li Di, Xiao Lihua

机构信息

Department of Ophthalmology, Affiliated Hospital of Weifang Medical College, Weifang, Shandong, China.

Institute of Rehabilitation Medicine of China, China Rehabilitation Science Institute, China Rehabilitation Research Center, Beijing, China.

出版信息

Onco Targets Ther. 2018 Dec 27;12:243-253. doi: 10.2147/OTT.S182118. eCollection 2019.

DOI:10.2147/OTT.S182118
PMID:30643422
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6312057/
Abstract

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 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. 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.

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.

摘要

目的

本研究旨在探讨VCP表达与眼眶B细胞淋巴瘤患者预后的关系，以及VCP下调对淋巴瘤细胞凋亡和侵袭能力的影响。

方法

我们招募了66例眼眶B细胞淋巴瘤患者。使用单克隆VCP抗体通过免疫组织化学法测定66份眼眶B细胞淋巴瘤样本中的VCP表达。根据免疫组织化学检测的VCP表达水平，我们从患者中选取了10例眼眶肿瘤石蜡组织。提取总RNA，并使用定量逆转录（qRT）PCR比较患者之间基因表达水平的差异。我们使用小干扰RNA（siRNA）敲低淋巴瘤细胞系Raji和SUDHL4中的VCP。分别应用qRT-PCR和蛋白质免疫印迹法检测VCP mRNA和蛋白表达。应用SUDHL48试验研究细胞增殖。应用Hoechst 33258染色和流式细胞术分析研究细胞凋亡。应用Transwell试验研究侵袭能力。采用生存分析评估预后价值。

结果

VCP表达水平与患者的分期、肿瘤分级和复发率相关。mRNA表达水平与眼眶B细胞淋巴瘤组织中的VCP表达水平一致。此外，生存分析显示，较低的VCP表达水平与眼眶B细胞淋巴瘤患者较长的总生存期相关。用siRNA下调VCP并不抑制细胞增殖。然而，它显著增加了凋亡并抑制了B细胞淋巴瘤细胞的侵袭。

结论

VCP表达在眼眶B细胞淋巴瘤的进展中起重要作用。VCP可能是预测眼眶B细胞淋巴瘤患者预后的有用标志物。VCP可能是眼眶B细胞淋巴瘤的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c6b/6312057/744ef477bf80/ott-12-243Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c6b/6312057/5e10b10a3dc5/ott-12-243Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c6b/6312057/6b1826bcca4d/ott-12-243Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c6b/6312057/09499ae19b4a/ott-12-243Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c6b/6312057/064d2762c9e3/ott-12-243Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c6b/6312057/692035345d7d/ott-12-243Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c6b/6312057/24ad968486cf/ott-12-243Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c6b/6312057/34443ccee960/ott-12-243Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c6b/6312057/744ef477bf80/ott-12-243Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c6b/6312057/5e10b10a3dc5/ott-12-243Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c6b/6312057/6b1826bcca4d/ott-12-243Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c6b/6312057/09499ae19b4a/ott-12-243Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c6b/6312057/064d2762c9e3/ott-12-243Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c6b/6312057/692035345d7d/ott-12-243Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c6b/6312057/24ad968486cf/ott-12-243Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c6b/6312057/34443ccee960/ott-12-243Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c6b/6312057/744ef477bf80/ott-12-243Fig8.jpg

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