Expression of the neuron-specific protein CHD5 is an independent marker of outcome in neuroblastoma.
Expression of the neuron-specific protein CHD5 is an independent marker of outcome in neuroblastoma.
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DOI：
10.1186/1476-4598-9-277
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发表时间：
2010-10-15
期刊：
影响因子：
37.3
通讯作者：
Lavarino C
中科院分区：
文献类型：
--
作者：
Garcia I;Mayol G;Rodríguez E;Suñol M;Gershon TR;Ríos J;Cheung NK;Kieran MW;George RE;Perez-Atayde AR;Casala C;Galván P;de Torres C;Mora J;Lavarino C
chromodomain，解旋酶DNA结合蛋白5（chromodomain，helicase DNA-binding protein 5，CHD 5）是一个潜在的肿瘤抑制基因，位于染色体1 p36，在高危神经母细胞瘤（neuroblastoma，NB）中经常缺失的区域。以往的研究表明，在正常神经组织和低危NB中存在CHD 5 mRNA，然而，尚未探索CHD 5蛋白的分布。本研究的目的是探讨CHD 5蛋白表达作为NB预后的免疫组化标志物。为此，我们分析了正常神经组织和神经母细胞瘤（NT）中CHD 5蛋白的表达。诱导化疗后，在一个高危肿瘤亚组中重新检查CHD 5基因和蛋白表达，以确定反映肿瘤反应的潜在变化。我们提供的证据表明，CHD 5是一种神经元特异性蛋白，在神经胶质细胞中不存在，在神经元类型之间具有不同的表达。在NT内，发现CHD 5免疫反应仅限于分化中的神经母细胞和神经节样细胞，而在未分化的神经母细胞和间质雪旺细胞中不存在。发现蛋白质和mRNA水平之间的相关性，表明CHD 5的转录调控。对90例原发性NT的免疫组化分析强调了CHD 5表达与有利的预后变量（诊断时年龄<12个月，临床分期低，组织学良好;所有P < 0.001），总生存期（OS）（P < 0.001）和无事件生存期（EFS）（P < 0.001）的强相关性。多变量分析显示，CHD 5预后价值与其他临床和生物学相关参数无关，因此可以代表NB结局的标志物，可以通过常规免疫组织化学进行检测。CHD 5的预后价值在32个NB肿瘤的独立盲组中得到证实（P < 0.001）。诱导化疗后CHD 5表达的重新激活主要见于具有诱导肿瘤细胞分化特征的高危肿瘤。值得注意的是，这些NB肿瘤显示出良好的临床反应和延长的患者生存期。神经元特异性蛋白质CHD 5可能代表NB的结果，可以通过常规免疫组织化学检测的标志物。化疗诱导的CHD 5表达的重建可能是治疗反应的替代标志物。
The chromodomain, helicase DNA-binding protein 5 (CHD5) is a potential tumor suppressor gene located on chromosome 1p36, a region recurrently deleted in high risk neuroblastoma (NB). Previous data have shown that CHD5 mRNA is present in normal neural tissues and in low risk NB, nevertheless, the distribution of CHD5 protein has not been explored. The aim of this study was to investigate CHD5 protein expression as an immunohistochemical marker of outcome in NB. With this purpose, CHD5 protein expression was analyzed in normal neural tissues and neuroblastic tumors (NTs). CHD5 gene and protein expression was reexamined after induction chemotherapy in a subset of high risk tumors to identify potential changes reflecting tumor response. We provide evidence that CHD5 is a neuron-specific protein, absent in glial cells, with diverse expression amongst neuron types. Within NTs, CHD5 immunoreactivity was found restricted to differentiating neuroblasts and ganglion-like cells, and absent in undifferentiated neuroblasts and stromal Schwann cells. Correlation between protein and mRNA levels was found, suggesting transcriptional regulation of CHD5. An immunohistochemical analysis of 90 primary NTs highlighted a strong association of CHD5 expression with favorable prognostic variables (age at diagnosis <12 months, low clinical stage, and favorable histology; P < 0.001 for all), overall survival (OS) (P < 0.001) and event-free survival (EFS) (P < 0.001). Multivariate analysis showed that CHD5 prognostic value is independent of other clinical and biologically relevant parameters, and could therefore represent a marker of outcome in NB that can be tested by conventional immunohistochemistry. The prognostic value of CHD5 was confirmed in an independent, blinded set of 32 NB tumors (P < 0.001). Reactivation of CHD5 expression after induction chemotherapy was observed mainly in those high risk tumors with induced tumor cell differentiation features. Remarkably, these NB tumors showed good clinical response and prolonged patient survival. The neuron-specific protein CHD5 may represent a marker of outcome in NB that can be tested by conventional immunohistochemistry. Re-establishment of CHD5 expression induced by chemotherapy could be a surrogate marker of treatment response.
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DOI：
10.1158/1078-0432.ccr-08-1815
发表时间：
2009-05-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Brodeur GM;Minturn JE;Ho R;Simpson AM;Iyer R;Varela CR;Light JE;Kolla V;Evans AE
通讯作者：
Evans AE
DOI：
10.1016/j.mrfmmm.2006.07.012
发表时间：
2007-05-01
影响因子：
2.3
作者：
Marfella, Concetta G. A.;Imbalzano, Anthony N.
通讯作者：
Imbalzano, Anthony N.
影响因子：
45.3
作者：
BRODEUR, GM;PRITCHARD, J;VOUTE, PA
通讯作者：
VOUTE, PA
影响因子：
64.5
作者：
Bagchi, Anindya;Papazoglu, Cristian;Mills, Alea A.
通讯作者：
Mills, Alea A.
影响因子：
2.7
作者：
Lavarino C;Garcia I;Mackintosh C;Cheung NK;Domenech G;Ríos J;Perez N;Rodríguez E;de Torres C;Gerald WL;Tuset E;Acosta S;Beleta H;de Alava E;Mora J
通讯作者：
Mora J