miRNA expression profiling enables risk stratification in archived and fresh neuroblastoma tumor samples.
miRNA expression profiling enables risk stratification in archived and fresh neuroblastoma tumor samples.
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DOI：
10.1158/1078-0432.ccr-11-0610
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发表时间：
2011-12-15
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通讯作者：
Vandesompele J
中科院分区：
文献类型：
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作者：
De Preter K;Mestdagh P;Vermeulen J;Zeka F;Naranjo A;Bray I;Castel V;Chen C;Drozynska E;Eggert A;Hogarty MD;Izycka-Swieszewska E;London WB;Noguera R;Piqueras M;Bryan K;Schowe B;van Sluis P;Molenaar JJ;Schramm A;Schulte JH;Stallings RL;Versteeg R;Laureys G;Van Roy N;Speleman F;Vandesompele J
更准确的预后评估对于进一步改善神经母细胞瘤（NB）患者风险相关治疗的选择至关重要。在这项研究中，我们旨在建立并验证NB患儿的预后miRNA特征，并在新鲜冷冻和存档的福尔马林固定石蜡包埋（FFPE）样本中进行测试。在两个临床病程差异最大的患者亚组中分析了430个人类成熟mirna。采用单因素logistic回归分析选择与NB患者生存相关的mirna。利用51个训练样本建立了25-miRNA基因签名，在179个测试样本上进行了测试，并在304个新鲜冷冻肿瘤样本和75个存档FFPE样本上进行了独立验证。无论是在总体人群还是在高危患者队列中，25-miRNA标记在无进展和总生存期方面显著区分试验患者（P < 0.0001）。多因素分析表明，在控制了当前危险因素后，miRNA特征是患者生存的独立预测因子。结果在外部验证集中得到证实。与先前发表的mRNA分类器相反，在一组75个FFPE神经母细胞瘤样本中，发现25-miRNA特征可预测患者生存。在本研究中，我们进行了迄今为止最大规模的NB miRNA表达研究，包括500多例NB患者。我们建立并验证了一个强大的miRNA分类器，能够使用新鲜冷冻和存档材料识别高风险NB患者队列，这些患者有更大的不良后果风险。
More accurate assessment of prognosis is important to further improve the choice of risk-related therapy in neuroblastoma (NB) patients. In this study, we aimed to establish and validate a prognostic miRNA signature for children with NB and tested it in both fresh frozen and archived formalin-fixed paraffin-embedded (FFPE) samples. Four hundred-thirty human mature miRNAs were profiled in two patient subgroups with maximally divergent clinical courses. Univariate logistic regression analysis was used to select miRNAs correlating with NB patient survival. A 25-miRNA gene signature was built using 51 training samples, tested on 179 test samples, and validated on an independent set of 304 fresh frozen tumor samples and 75 archived FFPE samples. The 25-miRNA signature significantly discriminates the test patients with respect to progression-free and overall survival (P < 0.0001), both in the overall population and in the cohort of high-risk patients. Multivariate analysis indicates that the miRNA signature is an independent predictor of patient survival after controlling for current risk factors. The results were confirmed in an external validation set. In contrast to a previously published mRNA classifier, the 25-miRNA signature was found to be predictive for patient survival in a set of 75 FFPE neuroblastoma samples. In this study, we present the largest NB miRNA expression study so far, including more than 500 NB patients. We established and validated a robust miRNA classifier, able to identify a cohort of high-risk NB patients at greater risk for adverse outcome using both fresh frozen and archived material.