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神经母细胞瘤中 MYCN、DDX1、TrkA 和 TrkC 基因转录本表达的预后影响。

Prognostic impact of MYCN, DDX1, TrkA, and TrkC gene transcripts expression in neuroblastoma.

机构信息

Laboratorio de Biologia Tumoral da Disciplina de Hematologia da Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil.

出版信息

Pediatr Blood Cancer. 2011 May;56(5):749-56. doi: 10.1002/pbc.22823. Epub 2010 Dec 9.

Abstract

BACKGROUND

The aims of this study were to define the mRNA expression profiles of MYCN, DDX1, TrkA, and TrkC in biopsy tumor samples from 64 Brazilian patients with neuroblastomas of different risk stages and to correlate altered expression with prognostic values.

PROCEDURE

Patients were retrospectively classified into low- (n = 11), intermediate- (n = 18), and high-risk (n = 35) groups using standard criteria. The mRNA levels of the above genes were measured by quantitative real-time polymerase chain reaction. Univariate analyses were performed and survival curves were plotted by the Kaplan-Meier method.

RESULTS

Of the 64 patients, 53% were female and 62.5% were older than 18 months. The 5-year overall survival (OS) for the entire cohort was 40.3%, with inferior median OS in patients identified in the intermediate- and high-risk groups. A significant difference in OS with respect to TrkA mRNA expression was found for the high-risk group vs. either the low- or intermediate-risk groups (P < 0.01, log rank test). Within the intermediate-risk group, neuroblastoma patients with positive TrkA mRNA expression had better clinical outcomes than patients with no TrkA transcript expression (P = 0.004). Another difference in OS was only found between the intermediate- and high-risk groups (P < 0.027, log rank test). No significant correlation of mRNA expression and survival outcome could be detected for the MYCN, DDX1.

CONCLUSIONS

Positive expression of TrkA mRNA may be a clinically useful addition to the current risk classification system, allowing the identification of NB tumors with favorable prognosis.

摘要

背景

本研究的目的是定义 64 例巴西不同危险度神经母细胞瘤患者活检肿瘤样本中 MYCN、DDX1、TrkA 和 TrkC 的 mRNA 表达谱,并将改变的表达与预后值相关联。

方法

患者采用标准标准回顾性分为低危(n=11)、中危(n=18)和高危(n=35)组。用定量实时聚合酶链反应测定上述基因的mRNA水平。进行单变量分析,并通过 Kaplan-Meier 法绘制生存曲线。

结果

在 64 例患者中,53%为女性,62.5%年龄大于 18 个月。整个队列的 5 年总生存率(OS)为 40.3%,中危和高危组患者的中位 OS 较差。高危组与低危或中危组相比,TrkA mRNA 表达的 OS 差异有统计学意义(P<0.01,对数秩检验)。在中危组中,TrkA mRNA 表达阳性的神经母细胞瘤患者比无 TrkA 转录表达的患者具有更好的临床结局(P=0.004)。仅在中危和高危组之间发现 OS 差异(P<0.027,对数秩检验)。未发现 MYCN、DDX1 mRNA 表达与生存结局的显著相关性。

结论

TrkA mRNA 的阳性表达可能是当前风险分类系统的有用补充,可识别具有良好预后的 NB 肿瘤。

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