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MicroRNA-30c 作为一种新型诊断生物标志物用于中枢神经系统原发性和继发性 B 细胞淋巴瘤。

MicroRNA-30c as a novel diagnostic biomarker for primary and secondary B-cell lymphoma of the CNS.

机构信息

Department of Medicine, Ruhr-University of Bochum, Knappschaftskrankenhaus Bochum-Langendreer, Bochum, Germany.

Department of Neurology, Hôpitaux Civils de Colmar, Colmar, France.

出版信息

J Neurooncol. 2018 May;137(3):463-468. doi: 10.1007/s11060-018-2749-0. Epub 2018 Jan 11.

Abstract

Primary lymphomas of the central nervous system (PCNSL) are highly aggressive tumors affecting exclusively the CNS, meninges, and eyes. PCNSL must be separated from secondary spread of systemic lymphoma to the CNS (SCNSL), which may occur at diagnosis or relapse of systemic lymphomas. At present, there are no valid methods to distinguish PCNSL from SCNSL based on tumor biopsy because of similar histological presentation. However, SCNSL and PCNSL are different in terms of prognosis and adequate therapy protocols. MicroRNA expression profiles of CSF samples collected from SCNSL and PCNSL patients were compared using microRNA arrays. MiR-30c revealed the largest differential expression and was selected for validation by RT-PCR on 61 CSF samples from patients with PCNSL and 14 samples from SCNSL. MiR-30c was significantly increased in patients with SCNSL compared to PCNSL (p < 0.001). MiR-30c levels in CSF enabled the differentiation of patients with PCNSL from SCNSL with an area under the curve (AUC) of 0.86, with a sensitivity of 90.9% and a specificity of 85.5%. Our data suggest that miR-30c detected in the CSF can serve as biomarker for distinction between PCNSL and SCNSL. The validation in a larger cohort is needed. With respect to its function, miR-30c may facilitate lymphoma cells to engraft into CNS by interaction with CELSR3 gene that controls the function of ependymal cilia and, thus, affects the circulation of CSF.

摘要

原发性中枢神经系统淋巴瘤(PCNSL)是一种高度侵袭性肿瘤,仅影响中枢神经系统、脑膜和眼睛。PCNSL 必须与系统性淋巴瘤向中枢神经系统的继发性扩散(SCNSL)区分开来,后者可能在诊断时或系统性淋巴瘤复发时发生。目前,由于组织学表现相似,基于肿瘤活检尚无有效方法将 PCNSL 与 SCNSL 区分开来。然而,PCNSL 和 SCNSL 在预后和适当的治疗方案方面存在差异。使用 microRNA 阵列比较了从 SCNSL 和 PCNSL 患者的 CSF 样本中收集的 microRNA 表达谱。MiR-30c 显示出最大的差异表达,并通过 RT-PCR 在 61 例 PCNSL 患者和 14 例 SCNSL 患者的 CSF 样本中进行验证。与 PCNSL 相比,SCNSL 患者的 miR-30c 明显增加(p<0.001)。MiR-30c 在 CSF 中的水平能够区分 PCNSL 和 SCNSL 患者,曲线下面积(AUC)为 0.86,灵敏度为 90.9%,特异性为 85.5%。我们的数据表明,CSF 中检测到的 miR-30c 可作为区分 PCNSL 和 SCNSL 的生物标志物。需要在更大的队列中进行验证。就其功能而言,miR-30c 可能通过与 CELSR3 基因相互作用,促进淋巴瘤细胞植入中枢神经系统,从而控制室管膜纤毛的功能,并影响 CSF 的循环。

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