The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma
The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma
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DOI：
10.1056/nejmoa012914
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发表时间：
2002-06-20
影响因子：
158.5
通讯作者：
Staudt, LM
中科院分区：
文献类型：
--
作者：
Rosenwald, A;Wright, G;Staudt, LM
背景：弥漫性大B细胞淋巴瘤患者化疗后的生存率受肿瘤分子特征的影响。我们使用这些淋巴瘤的基因表达谱，以开发一个分子预测survival.Methods：从240例患者的弥漫性大B细胞淋巴瘤的活检样本进行了检查基因表达与使用DNA微阵列和基因组异常分析。具有独特基因表达谱的亚组是根据层次聚类定义的。一个风险的分子预测器是使用与160例患者的初步组中的生存相关的表达模式的基因构建的，然后在80例患者的验证组中进行测试。这个预测的准确性进行了比较，与国际预后index.Results：三个基因表达亚组-生殖中心B细胞样，活化B细胞样，3型弥漫性大B细胞淋巴瘤-被确定。两个常见的致癌事件，弥漫性大B细胞淋巴瘤，bcl-2易位和c-rel扩增，只在生殖中心B细胞样亚组检测。该亚组患者的5年生存率最高。为了确定其他决定预后的分子因素，我们在初步研究的患者中寻找具有与生存相关的表达模式的个体基因。这些基因中的大多数属于四种基因表达特征，即生殖中心B细胞、增殖细胞、淋巴结中的反应性基质和免疫细胞或主要组织相容性复合物II类复合物。我们使用17个基因来构建化疗后总生存率的预测因子。这个基因为基础的预测和国际预后指数是独立的预后indicator.Conclusions：DNA微阵列可以用来制定一个分子预测化疗后的生存弥漫性大B细胞淋巴瘤。
Background: The survival of patients with diffuse large-B-cell lymphoma after chemotherapy is influenced by molecular features of the tumors. We used the gene-expression profiles of these lymphomas to develop a molecular predictor of survival.Methods: Biopsy samples of diffuse large-B-cell lymphoma from 240 patients were examined for gene expression with the use of DNA microarrays and analyzed for genomic abnormalities. Subgroups with distinctive gene-expression profiles were defined on the basis of hierarchical clustering. A molecular predictor of risk was constructed with the use of genes with expression patterns that were associated with survival in a preliminary group of 160 patients and was then tested in a validation group of 80 patients. The accuracy of this predictor was compared with that of the international prognostic index.Results: Three gene-expression subgroups -- germinal-center B-cell-like, activated B-cell-like, and type 3 diffuse large-B-cell lymphoma -- were identified. Two common oncogenic events in diffuse large-B-cell lymphoma, bcl-2 translocation and c-rel amplification, were detected only in the germinal-center B-cell-like subgroup. Patients in this subgroup had the highest five-year survival rate. To identify other molecular determinants of outcome, we searched for individual genes with expression patterns that correlated with survival in the preliminary group of patients. Most of these genes fell within four gene-expression signatures characteristic of germinal-center B cells, proliferating cells, reactive stromal and immune cells in the lymph node, or major-histocompatibility-complex class II complex. We used 17 genes to construct a predictor of overall survival after chemotherapy. This gene-based predictor and the international prognostic index were independent prognostic indicators.Conclusions: DNA microarrays can be used to formulate a molecular predictor of survival after chemotherapy for diffuse large-B-cell lymphoma.