Department of Neurology, University Hospital Zurich, 8091 Zurich, Switzerland.
Chair for Clinical Bioinformatics, Saarland University, 66123 Saarbrücken, Germany.
Eur J Cancer. 2015 Feb;51(3):382-90. doi: 10.1016/j.ejca.2014.10.028. Epub 2014 Dec 17.
Despite improved therapeutic regimens, primary CNS lymphoma (PCNSL) remains a therapeutic challenge. A prognostic classification of PCNSL patients may represent an important step towards optimised patient-adapted therapy. However, only higher age and low Karnofsky Performance Status (KPS) have repeatedly been reported to be associated with shorter overall survival (OS). Here we characterised microRNA (miRNA) fingerprints in the blood of PCNSL patients with short-term survival (STS) versus long-term survival (LTS) to assess their potential as novel prognostic biomarkers. Blood was collected from patients enrolled in the G-PCNSL-SG1 trial, a phase III study for patients with newly diagnosed PCNSL. miRNAs were extracted from the blood and analysed by next generation sequencing. The STS group comprised 20 patients with a median OS of 3 months and was compared to 20 LTS patients with a median OS of 55 months. The cohorts were balanced for age and KPS. Twelve annotated miRNAs were significantly deregulated between the two groups. Among them, miR-151a-5p and miR-151b exhibited the most prominent differences. Importantly, the combination of several miRNA allowed for a good separation between short- and long-term survivors with maximal Area Under Curve (AUC) above 0.75. Besides the known miRNAs we identified putative novel miRNA candidates with potential regulatory influence of PCNSL. Finally, the differential regulation of the most promising candidate miRNAs was confirmed by real-time polymerase chain reaction (PCR) in a validation cohort consisting of 20 STS and LTS patients. In conclusion, peripheral blood miRNA expression patterns hold promise as a prognostic tool in PCNSL patients.
尽管治疗方案有所改善，但原发性中枢神经系统淋巴瘤（PCNSL）仍然是一个治疗挑战。对 PCNSL 患者进行预后分类可能是朝着优化患者适应性治疗迈出的重要一步。然而，只有更高的年龄和较低的 Karnofsky 表现状态（KPS）被反复报道与总生存期（OS）较短相关。在这里，我们对短期生存（STS）与长期生存（LTS）的 PCNSL 患者的血液中的 microRNA（miRNA）指纹进行了特征描述，以评估其作为新型预后生物标志物的潜力。采集了参加 G-PCNSL-SG1 试验的患者的血液，该试验是一项针对新诊断的 PCNSL 患者的 III 期研究。从血液中提取 miRNA 并进行下一代测序分析。STS 组包括 20 名患者，中位 OS 为 3 个月，与 20 名 LTS 患者（中位 OS 为 55 个月）进行比较。这两个队列在年龄和 KPS 方面是平衡的。两组间有 12 个注释 miRNA 明显失调。其中，miR-151a-5p 和 miR-151b 表现出最显著的差异。重要的是，几个 miRNA 的组合可以很好地区分短期和长期幸存者，最大 AUC 高于 0.75。除了已知的 miRNA，我们还鉴定了具有潜在调控 PCNSL 作用的新的 miRNA 候选物。最后，通过包含 20 名 STS 和 LTS 患者的验证队列的实时聚合酶链反应（PCR）证实了最有前途的候选 miRNA 的差异调节。总之，外周血 miRNA 表达模式有望成为 PCNSL 患者的预后工具。
