Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Pediatr Blood Cancer. 2012 Aug;59(2):226-32. doi: 10.1002/pbc.23343. Epub 2011 Oct 11.
Neuroblastomas (NBs) are characterized by clinical heterogeneity, from spontaneous regression to relentless progression. The pattern of NTRK family gene expression contributes to these disparate behaviors. TrkA/NTRK1 is expressed in favorable NBs that regress or differentiate, whereas TrkB/NTRK2 and its ligand brain-derived neurotrophic factor (BDNF) are co-expressed in unfavorable NBs, representing an autocrine survival pathway. We determined the significance of NTRK family gene expression in a large, representative set of primary NBs.
We analyzed the expression of the following genes in 814 NBs using quantitative real-time reverse transcriptase polymerase chain reaction (RT-PCR): NTRK1, NTRK2, NTRK3, P75/NGFR, nerve growth factor (NGF), BDNF, IGFR1, and EGFR. Expression (high vs. low) was dichotomized by median expression value and compared to clinical and biological variables as well as outcome.
High NTRK1 expression was strongly correlated with favorable age, stage, MYCN status, histology, ploidy, risk group, and outcome (P < 0.0001 for all). However, it did not add significantly to the panel of prognostic variables currently used for cooperative group trials. NTRK2 expression was associated with risk factors but not with outcome. High NGF expression was also associated with most risk factors and weakly with unfavorable outcome.
High expression of NTRK1 is strongly associated with favorable risk factors and outcome in a large, representative population of NB patients. It did not add significantly to the current risk prediction algorithm, but it may contribute to future expression classifiers. Indeed, prospective assessment of NTRK1 and NTRK2 expression will identify tumors that would be candidates for NTRK-targeted therapy, either alone or in combination with conventional agents.
神经母细胞瘤（NB）的临床表型具有异质性，从自发消退到进行性恶化。NTRK 家族基因表达模式促成了这些不同的行为。TrkA/NTRK1 在自发消退或分化的有利 NB 中表达，而 TrkB/NTRK2 和其配体脑源性神经营养因子（BDNF）共同表达在不利的 NB 中，代表了一种自分泌生存途径。我们在一组大型、代表性的原发性 NB 中确定了 NTRK 家族基因表达的意义。
我们使用定量实时逆转录聚合酶链反应（RT-PCR）分析了 814 例 NB 中以下基因的表达：NTRK1、NTRK2、NTRK3、P75/NGFR、神经生长因子（NGF）、BDNF、IGFR1 和 EGFR。通过中位表达值将表达（高与低）进行二分类，并与临床和生物学变量以及预后进行比较。
高 NTRK1 表达与有利的年龄、分期、MYCN 状态、组织学、倍性、风险组和预后密切相关（所有 P<0.0001）。然而，它并没有显著增加目前用于合作组试验的预后变量组合。NTRK2 表达与危险因素相关，但与预后无关。高 NGF 表达也与大多数危险因素相关，与不良预后相关较弱。
在一组大型、代表性的 NB 患者人群中，高 NTRK1 表达与有利的风险因素和预后密切相关。它没有显著增加当前的风险预测算法，但可能有助于未来的表达分类器。事实上，前瞻性评估 NTRK1 和 NTRK2 表达将确定可能成为 NTRK 靶向治疗候选的肿瘤，无论是单独使用还是与常规药物联合使用。
