A gene expression signature for high-risk multiple myeloma
A gene expression signature for high-risk multiple myeloma
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DOI：
10.1038/leu.2012.127
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发表时间：
2012-11-01
期刊：
影响因子：
11.4
通讯作者：
Sonneveld, P.
中科院分区：
文献类型：
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作者：
Kuiper, R.;Broyl, A.;Sonneveld, P.
有一个强烈的需求，以更好地预测新诊断的多发性骨髓瘤（MM）患者的生存。由于基因表达谱（GEP）反映了个体患者中MM的生物学特征，因此我们基于GEP建立了预后特征。从HOVON 65/GMMG-HD 4试验（n = 290）中纳入的新诊断MM患者获得的GEP用作训练数据。使用该集合，通过结合模拟退火的监督主成分分析生成92个基因的预后标记（EMC-92-基因标记）。EMC-92-基因签名的性能在新诊断（总治疗（TT）2，n = 351; TT 3，n = 142; MRC-IX，n = 247）和复发患者（APEX，n = 264）的独立验证集中得到证实。在所有组中，通过EMC-92基因特征定义为高风险的患者显示出明显降低的总生存期（OS），风险比（HR）为3.40（95%置信区间（CI）：2.19-5.29），TT 2研究为5.23 TT 3研究为2.38（95% CI：1.65-3.43），APEX研究为3.01（95% CI：2.06-4.39）（P
There is a strong need to better predict the survival of patients with newly diagnosed multiple myeloma (MM). As gene expression profiles (GEPs) reflect the biology of MM in individual patients, we built a prognostic signature based on GEPs. GEPs obtained from newly diagnosed MM patients included in the HOVON65/GMMG-HD4 trial (n = 290) were used as training data. Using this set, a prognostic signature of 92 genes (EMC-92-gene signature) was generated by supervised principal component analysis combined with simulated annealing. Performance of the EMC-92-gene signature was confirmed in independent validation sets of newly diagnosed (total therapy (TT) 2, n = 351; TT3, n = 142; MRC-IX, n = 247) and relapsed patients (APEX, n = 264). In all the sets, patients defined as high-risk by the EMC-92-gene signature show a clearly reduced overall survival (OS) with a hazard ratio (HR) of 3.40 (95% confidence interval (CI): 2.19-5.29) for the TT2 study, 5.23 (95% CI: 2.46-11.13) for the TT3 study, 2.38 (95% CI: 1.65-3.43) for the MRC-IX study and 3.01 (95% CI: 2.06-4.39) for the APEX study (P