Prediction of survival in follicular lymphoma based on molecular features of tumor-infiltrating immune cells
Prediction of survival in follicular lymphoma based on molecular features of tumor-infiltrating immune cells
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DOI：
10.1056/nejmoa041869
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发表时间：
2004-11-18
影响因子：
158.5
通讯作者：
Staudt, LM
中科院分区：
文献类型：
--
作者：
Dave, SS;Wright, G;Staudt, LM
背景：滤泡性淋巴瘤患者在诊断后的生存期可能少于1年，也可能超过20年。我们使用诊断时获得的肿瘤活检标本的基因表达谱来开发生存时间的分子预测因子。方法：对未经治疗的滤泡性淋巴瘤患者的191例活检标本进行基因表达谱分析。在95个标本的训练集中，使用监督方法来发现与生存长度相关的表达模式。从这些基因构建了一个生存的分子预测因子，并在96个标本的独立测试集中进行了验证。结果：预测生存长度的单个基因根据其在训练集中的表达将其分组为基因表达签名，并使用两个这样的签名构建生存预测器。这两个特征允许将测试集中的标本患者分为四个四分位数，其中位生存期（13.6年、11.1年、10.8年和3.9年）差异很大，独立于临床预后变量。流式细胞术显示这些特征反映了非恶性肿瘤浸润性免疫细胞的基因表达。结论：滤泡性淋巴瘤患者的生存时间与诊断时肿瘤中存在的非恶性免疫细胞的分子特征有关。
Background:Patients with follicular lymphoma may survive for periods of less than 1 year to more than 20 years after diagnosis. We used gene-expression profiles of tumor-biopsy specimens obtained at diagnosis to develop a molecular predictor of the length of survival.Methods:Gene-expression profiling was performed on 191 biopsy specimens obtained from patients with untreated follicular lymphoma. Supervised methods were used to discover expression patterns associated with the length of survival in a training set of 95 specimens. A molecular predictor of survival was constructed from these genes and validated in an independent test set of 96 specimens.Results:Individual genes that predicted the length of survival were grouped into gene-expression signatures on the basis of their expression in the training set, and two such signatures were used to construct a survival predictor. The two signatures allowed patients with specimens in the test set to be divided into four quartiles with widely disparate median lengths of survival (13.6, 11.1, 10.8, and 3.9 years), independently of clinical prognostic variables. Flow cytometry showed that these signatures reflected gene expression by nonmalignant tumor-infiltrating immune cells.Conclusions:The length of survival among patients with follicular lymphoma correlates with the molecular features of nonmalignant immune cells present in the tumor at diagnosis.