Identification of DDX39A as a Potential Biomarker for Unfavorable Neuroblastoma Using a Proteomic Approach
Identification of DDX39A as a Potential Biomarker for Unfavorable Neuroblastoma Using a Proteomic Approach
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使用蛋白质组学方法鉴定 DDX39A 作为不利神经母细胞瘤的潜在生物标志物
DOI：
10.1002/pbc.25778
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发表时间：
2016
期刊：
影响因子：
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通讯作者：
Kusunoki M
中科院分区：
文献类型：
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作者：
Otake K;Uchida K;Ide S;Kobayashi Y;Kobayashi I;Kusunoki M
背景不良神经母细胞瘤(NB)的恶性潜能取决于未分化状态。本研究的目的是寻找一种新的与NBIN体外未分化状态相关的生物标志物，并评价其预后意义。鉴定出的蛋白质经多反应监测(MRM)验证，并用Western印迹分析进行鉴定。结果在未分化的NB细胞中检测到12种蛋白的表达，其中包括ATP依赖的RNA解旋酶(DDX39A)。在未分化的IMR-32(P=0.002)和LA-N-1(P<；0.001)细胞中检测到明显高水平的DDX39A多肽。Western印迹分析显示，未分化的IMR-32(P=0.02)和LA-N-1(P=0.025)细胞中DDX39A的表达显著增加。免疫组化结果显示，DDX39A在预后不良的原发肿瘤组织中高表达，单因素和多因素生存分析显示，DDX39A的表达可作为一个独立的预后不良因素(P=0.027)。结论从蛋白质组学角度分析，DDX39A是一种潜在的预后不良因素。检测神经母细胞瘤组织中DDX39A蛋白的表达可能为肿瘤的进一步亚型提供补充的预后信息。
BackgroundMalignant potential in unfavorable neuroblastoma (NB) is dependent on an undifferentiated status. The aim of this study was to identify a novel biomarker associated with the undifferentiated status of NBin vitroand to evaluate its prognostic implication.ProcedureShotgun proteomic analysis was performed in undifferentiated and alltrans‐retinoic acid induced differentiated NB cellsin vitro. An identified protein was verified by multiple reaction monitoring (MRM) and evaluated by Western blot analysis. Immunohistochemistry (IHC) was used to examine the expression of the identified protein in 33 primary NB tissues.ResultsTwelve proteins, including ATP‐dependent RNA helicase (DDX39A), were only detected in undifferentiated NB cells. A peptide of DDX39A was detected at a significantly higher level in undifferentiated IMR‐32 (P= 0.002) and LA‐N‐1 (P< 0.001) cells by MRM. Western blot analysis revealed that DDX39A expression was significantly higher in undifferentiated IMR‐32 (P= 0.02) and LA‐N‐1 (P= 0.025) cells. IHC demonstrated that DDX39A was highly expressed in the primary tumor tissues of patients with poor prognosis, and univariate and multivariate survival analyses showed that DDX39A expression could be an independent unfavorable prognostic factor (P= 0.027).ConclusionsDDX39A is a potential biomarker for unfavorable NB using a proteomic approach. Evaluation of DDX39A protein expression in NB tumor tissues may provide complementary prognostic information for further subclassification of these tumors.