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神经母细胞瘤患者的预后、肿瘤分化以及ERK激活与泛素连接酶UBE4B的表达水平相关。

Neuroblastoma patient outcomes, tumor differentiation, and ERK activation are correlated with expression levels of the ubiquitin ligase UBE4B.

作者信息

Woodfield Sarah E, Guo Rong Jun, Liu Yin, Major Angela M, Hollingsworth Emporia Faith, Indiviglio Sandra, Whittle Sarah B, Mo Qianxing, Bean Andrew J, Ittmann Michael, Lopez-Terrada Dolores, Zage Peter E

机构信息

Department of Pediatrics, Section of Hematology/Oncology, Baylor College of Medicine, Houston, TX, USA.

Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA; Department of Pathology, University of Alabama Birmingham, Birmingham, AL, USA.

出版信息

Genes Cancer. 2016 Jan;7(1-2):13-26. doi: 10.18632/genesandcancer.97.

DOI:10.18632/genesandcancer.97
PMID:27014418
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4773702/
Abstract

BACKGROUND

UBE4B is an E3/E4 ubiquitin ligase whose gene is located in chromosome 1p36.22. We analyzed the associations of UBE4B gene and protein expression with neuroblastoma patient outcomes and with tumor prognostic features and histology.

METHODS

We evaluated the association of UBE4B gene expression with neuroblastoma patient outcomes using the R2 Platform. We screened neuroblastoma tumor samples for UBE4B protein expression using immunohistochemistry. FISH for UBE4B and 1p36 deletion was performed on tumor samples. We then evaluated UBE4B expression for associations with prognostic factors and with levels of phosphorylated ERK in neuroblastoma tumors and cell lines.

RESULTS

Low UBE4B gene expression is associated with poor outcomes in patients with neuroblastoma and with worse outcomes in all patient subgroups. UBE4B protein expression was associated with neuroblastoma tumor differentiation, and decreased UBE4B protein levels were associated with high-risk features. UBE4B protein levels were also associated with levels of phosphorylated ERK.

CONCLUSIONS

We have demonstrated associations between UBE4B gene expression and neuroblastoma patient outcomes and prognostic features. Reduced UBE4B protein expression in neuroblastoma tumors was associated with high-risk features, a lack of differentiation, and with ERK activation. These results suggest UBE4B may contribute to the poor prognosis of neuroblastoma tumors with 1p36 deletions and that UBE4B expression may mediate neuroblastoma differentiation.

摘要

背景

UBE4B是一种E3/E4泛素连接酶，其基因位于1号染色体的1p36.22区域。我们分析了UBE4B基因及蛋白表达与神经母细胞瘤患者预后、肿瘤预后特征和组织学之间的关联。

方法

我们使用R2平台评估UBE4B基因表达与神经母细胞瘤患者预后的关联。我们通过免疫组织化学筛选神经母细胞瘤肿瘤样本中的UBE4B蛋白表达。对肿瘤样本进行UBE4B和1p36缺失的荧光原位杂交检测。然后我们评估UBE4B表达与神经母细胞瘤肿瘤及细胞系中预后因素和磷酸化ERK水平的关联。

结果

UBE4B基因低表达与神经母细胞瘤患者的不良预后相关，且在所有患者亚组中预后更差。UBE4B蛋白表达与神经母细胞瘤肿瘤分化相关，UBE4B蛋白水平降低与高危特征相关。UBE4B蛋白水平也与磷酸化ERK水平相关。

结论

我们已经证明了UBE4B基因表达与神经母细胞瘤患者预后及预后特征之间的关联。神经母细胞瘤肿瘤中UBE4B蛋白表达降低与高危特征、缺乏分化以及ERK激活相关。这些结果表明UBE4B可能导致伴有1p36缺失的神经母细胞瘤肿瘤预后不良，且UBE4B表达可能介导神经母细胞瘤分化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78a8/4773702/3dce0d57993e/ganc-07-013-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78a8/4773702/61cd21a25b65/ganc-07-013-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78a8/4773702/6ec98d6744fd/ganc-07-013-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78a8/4773702/3a5152c4583f/ganc-07-013-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78a8/4773702/536b61422219/ganc-07-013-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78a8/4773702/37b21eea54f9/ganc-07-013-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78a8/4773702/3dce0d57993e/ganc-07-013-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78a8/4773702/61cd21a25b65/ganc-07-013-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78a8/4773702/e1677ae28acf/ganc-07-013-g002a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78a8/4773702/6ec98d6744fd/ganc-07-013-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78a8/4773702/3a5152c4583f/ganc-07-013-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78a8/4773702/536b61422219/ganc-07-013-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78a8/4773702/37b21eea54f9/ganc-07-013-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78a8/4773702/3dce0d57993e/ganc-07-013-g007.jpg

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