Expression of the neurotrophin receptor TrkB is associated with unfavorable outcome in Wilms' tumor
Expression of the neurotrophin receptor TrkB is associated with unfavorable outcome in Wilms' tumor
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DOI：
10.1200/jco.2001.19.3.689
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发表时间：
2001-02-01
影响因子：
45.3
通讯作者：
Evans, AE
中科院分区：
文献类型：
--
作者：
Eggert, A;Grotzer, MA;Evans, AE
目的：神经营养因子及其受体调节神经细胞的增殖、分化和死亡，并参与神经母细胞瘤和髓母细胞瘤的发病机制和预后。酪氨酸激酶（Trk）受体也在神经外组织中表达。患者和方法：为了研究神经营养因子受体和配体在Wilms肿瘤（Wt）中的作用，我们在39例原发性Wt患者中采用半定量双相逆转录酶聚合酶链式反应测定了它们的表达，并使用Cox回归分析将mRNA表达水平与临床变量进行比较。结果：高水平表达全长TrkB mRNA （TrkBfull）的Wi患儿的死亡风险明显高于TrkBfull表达很少或没有表达的患儿（风险比为9.7;P = 0.02）。TrkBfull低表达和高表达患者的5年无复发生存率分别为100%和65% （P < 0.003）。相反，与TrkBtrunc水平较低的儿童相比，功能失活截断TrkB受体（TrkBtrunc） mRNA表达水平较高的肿瘤儿童的生存机会更大（风险比，0.08;P = 0.005）。TrkBtrunc高水平和低水平患者的5年无复发生存率分别为95%和68% （P = 0.01）。经肿瘤分期调整后，TrkBfull和TrkBtrunc的风险比仍然显著（P = 0.01和P = 0.017）。所有TrkB高表达的WTs也表达脑源性神经生长因子配体。结论：TrkBfull在WT中的表达与较差的预后相关，可能是因为它提供了一种自分泌的生存途径。相反，TrkBtrunc表达与良好的结果相关，可能是由于显性负作用的结果。(C) 2001年美国临床肿瘤学会。
Purpose: Neurotrophins and their receptors regulate the proliferation, differentiation, and death of neuronal cells, and they have been implicated in the pathogenesis and prognosis of neuroblastomas and medulloblastomas. Tyrosine kinase (Trk) receptors also are expressed in extraneural tissues.Patients and Methods: To study the role of neurotrophin receptors and ligands in Wilms' tumor (Wt), we determined their expression by semi-quantitative duplex reverse transcriptase polymerase chain reaction in 39 patients with primary WT. Comparison of mRNA expression levels with clinical variables was performed by use of Cox regression analysis.Results: Children with Wi that expressed high levels of full-length TrkB mRNA (TrkBfull) had ct significantly greater risk of death than children whose tumors had little or no TrkBfull expression (hazard ratio, 9.7; P = .02). The 5-year relapse free sunvival was 100% versus 65% for patients with low versus high tumor expression of TrkBfull (P < .003). Conversely, children with tumors that expressed high mRNA levels of a functionally inactive truncated TrkB receptor (TrkBtrunc) had a greater chance of survival than children with low levers of TrkBtrunc (hazard ratio, 0.08; P = .005). The 5-year relapse-free survival was 95% versus 68% for patients with high versus low levels of TrkBtrunc (P = .01). The hazard ratios for TrkBfull and TrkBtrunc remained significant after they were adjusted for tumor stage (P =.01 and P = .017, respectively). All WTs with high levels of TrkB expression also expressed the brain-derived nerve growth factor ligand.Conclusion: Expression of TrkBfull in WT is associated with worse outcome, perhaps because it provides an autocrine survival pathway. Conversely, TrkBtrunc expression is associated with excellent outcome, perhaps as a result of a dominant negative effect. (C) 2001 by American Society of Clinical Oncology.