Lymphoma Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
Blood. 2011 Jul 28;118(4):1034-40. doi: 10.1182/blood-2010-11-321554. Epub 2011 Jun 1.
Diffuse large B-cell lymphoma (DLBCL) prognostication requires additional biologic markers. miRNAs may constitute markers for cancer diagnosis, outcome, or therapy response. In the present study, we analyzed the miRNA expression profile in a retrospective multicenter series of 258 DLBCL patients uniformly treated with chemoimmunotherapy. Findings were correlated with overall survival (OS) and progression-free survival (PFS). miRNA and gene-expression profiles were studied using microarrays in an initial set of 36 cases. A selection of miRNAs associated with either DLBCL molecular subtypes (GCB/ABC) or clinical outcome were studied by multiplex RT-PCR in a test group of 240 cases with available formalin-fixed, paraffin-embedded (FFPE) diagnostic samples. The samples were divided into a training set (123 patients) and used to derive miRNA-based and combined (with IPI score) Cox regression models in an independent validation series (117 patients). Our model based on miRNA expression predicts OS and PFS and improves upon the predictions based on clinical variables. Combined models with IPI score identified a high-risk group of patients with a 2-year OS and a PFS probability of < 50%. In summary, a precise miRNA signature is associated with poor clinical outcome in chemoimmunotherapy-treated DLBCL patients. This information improves upon IPI-based predictions and identifies a subgroup of candidate patients for alternative therapeutic regimens.
弥漫性大 B 细胞淋巴瘤（DLBCL）的预后需要额外的生物学标志物。miRNA 可能成为癌症诊断、预后或治疗反应的标志物。在本研究中，我们分析了 258 例经化疗免疫治疗的回顾性多中心系列患者的 miRNA 表达谱。研究结果与总生存期（OS）和无进展生存期（PFS）相关。使用微阵列对初始 36 例患者的 miRNA 和基因表达谱进行了研究。在可获得福尔马林固定、石蜡包埋（FFPE）诊断样本的 240 例测试组中，通过多重 RT-PCR 研究了与 DLBCL 分子亚型（GCB/ABC）或临床结果相关的选定 miRNA。将这些样本分为训练集（123 例患者），并在独立验证系列（117 例患者）中用于推导基于 miRNA 的和组合（与 IPI 评分）Cox 回归模型。我们基于 miRNA 表达的模型可预测 OS 和 PFS，并提高了基于临床变量的预测。与 IPI 评分相结合的模型确定了一个 2 年 OS 和 PFS 概率<50%的高危患者组。总之，在接受化疗免疫治疗的 DLBCL 患者中，精确的 miRNA 特征与不良临床结局相关。该信息可提高基于 IPI 的预测，并确定了候选患者的亚组，用于替代治疗方案。
