Prediction of survival in diffuse large B-cell lymphoma based on the expression of 2 genes reflecting tumor and microenvironment
Prediction of survival in diffuse large B-cell lymphoma based on the expression of 2 genes reflecting tumor and microenvironment
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DOI：
10.1182/blood-2011-03-345272
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发表时间：
2011-08-04
期刊：
影响因子：
20.3
通讯作者：
Levy, Ronald
中科院分区：
文献类型：
--
作者：
Alizadeh, Ash A.;Gentles, Andrew J.;Levy, Ronald
一些基因表达特征预测弥漫性大b细胞淋巴瘤（DLBCL）的生存，但缺乏实用的基因组规模分析方法，限制了其在临床实践中的应用。我们建立并验证了一个简单的模型，使用肿瘤细胞表达的一个基因和宿主免疫细胞表达的另一个基因，评估临床国际预后指数（IPI）的附加预后价值。LIM结构域2 （LMO2）被证实是存活和“生发中心B细胞样”亚型的独立预测因子。来自DLBCL微环境的肿瘤坏死因子受体超家族成员9 （TNFRSF9）在与LMO2的双变量组合中表达最好。对95例DLBCL患者TNFRSF9组织表达的研究显示，表达仅限于浸润T细胞。整合这两个基因的模型独立于“细胞起源”分类、“基质特征”、IPI，并增加了IPI的预测能力。整合这些基因与IPI的综合评分在545名DLBCL患者的3个独立队列中表现良好，在147名DLBCL患者的常规福尔马林固定标本的简单分析中也表现良好。我们得出结论，肿瘤细胞表达的单个基因（LMO2）和免疫微环境表达的单个基因（TNFRSF9）的测量有力地预测了DLBCL患者的总生存期。（血液，2011;118(5):1350-1358）
Several gene-expression signatures predict survival in diffuse large B-cell lymphoma (DLBCL), but the lack of practical methods for genome-scale analysis has limited translation to clinical practice. We built and validated a simple model using one gene expressed by tumor cells and another expressed by host immune cells, assessing added prognostic value to the clinical International Prognostic Index (IPI). LIM domain only 2 (LMO2) was validated as an independent predictor of survival and the "germinal center B cell-like" subtype. Expression of tumor necrosis factor receptor superfamily member 9 (TNFRSF9) from the DLBCL microenvironment was the best gene in bivariate combination with LMO2. Study of TNFRSF9 tissue expression in 95 patients with DLBCL showed expression limited to infiltrating T cells. A model integrating these 2 genes was independent of "cell-of-origin" classification, "stromal signatures," IPI, and added to the predictive power of the IPI. A composite score integrating these genes with IPI per-formed well in 3 independent cohorts of 545 DLBCL patients, as well as in a simple assay of routine formalin-fixed specimens from a new validation cohort of 147 patients with DLBCL. We conclude that the measurement of a single gene expressed by tumor cells (LMO2) and a single gene expressed by the immune microenvironment (TNFRSF9) powerfully predicts overall survival in patients with DLBCL. (Blood. 2011; 118(5): 1350-1358)