Prognostic significance of gene expression profiles of metastatic neuroblastomas lacking MYCN gene amplification
Prognostic significance of gene expression profiles of metastatic neuroblastomas lacking MYCN gene amplification
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DOI：
10.1093/jnci/djj330
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发表时间：
2006-09-06
影响因子：
10.3
通讯作者：
Seeger, Robert C.
中科院分区：
文献类型：
--
作者：
Asgharzadeh, Shahab;Pique-Regi, Roger;Seeger, Robert C.
背景缺乏MYCN基因扩增的转移性神经母细胞瘤的侵袭性随年龄而变化--在小于12个月的患者中诊断时侵袭性最低，在大于24个月的患者中诊断时侵袭性最高。然而，诊断时的年龄并不总是与患者生存相关。我们研究了使用基因表达谱对诊断时没有MYCN基因扩增的转移性神经母细胞瘤进行分子分类是否可以提高疾病进展风险的预测。研究方法：我们使用Affyssin微阵列来确定102例未经治疗的原发性神经母细胞瘤的基因表达谱，这些神经母细胞瘤没有MYCN基因扩增，这些神经母细胞瘤是从诊断时年龄在0.1到151个月的儿童中获得的。设计了一种使用对角线性判别分析的监督方法来建立预测疾病进展风险的多基因模型。使用嵌套交叉验证、排列分析和在疾病进展时获得的另外15个肿瘤的基因表达数据来评估模型的准确性。结果如下：使用55个基因的表达谱模型定义了一个肿瘤标记，该标记将两组患者从诊断时年龄大于12个月的患者中区分出来，这些患者临床上被分类为具有高风险疾病，无进展生存率（PFS）为16%。（95%置信区间[CI] = 8%-28%），PFS率为79%（95% CI = 57%-91%）（P
Background. The aggressiveness of metastatic neuroblastomas that lack MYCN gene amplification varies with age-they are least aggressive when diagnosed in patients younger than 12 months and most aggressive when diagnosed in patients older than 24 months. However, age at diagnosis is not always associated with patient survival. We examined whether molecular classification of metastatic neuroblastomas without MYCN gene amplification at diagnosis using gene expression profiling could improve the prediction of risk of disease progression. Methods: We used Affymetrix microarrays to determine the gene expression profiles of 102 untreated primary neuroblastomas without MYCN gene amplification obtained from children whose ages at diagnosis ranged from 0.1 to 151 months. A supervised method using diagonal linear discriminant analysis was devised to build a multigene model for predicting risk of disease progression. The accuracy of the model was evaluated using nested cross-validations, permutation analyses, and gene expression data from 15 additional tumors obtained at disease progression. Results: An expression profile model using 55 genes defined a tumor signature that distinguished two groups of patients from among those older than 12 months at diagnosis and clinically classified as having high-risk disease, those with a progression-free survival (PFS) rate of 16% (95% confidence interval [CI] = 8% to 28%), and those with a PFS rate of 79% (95% Cl = 57% to 91%) (P