在 GBM 患者血清外泌体中发现的小非编码 RNA 标志物作为一种诊断工具。
A small noncoding RNA signature found in exosomes of GBM patient serum as a diagnostic tool.
机构信息
Instituto Biodonostia and Hospital Universitario Donostia, San Sebastian, Spain (L.M., N.S., C.B., I.R., A.M., A.L.-M.); Center for Applied Medical Research (CIMA), Pamplona, Spain (E.G., V.S.); Clínica Universidad de Navarra, Pamplona, Spain (J.G.P-L., M.G-H., P.J., S.T., R.D.-V., J.R., A.G., E.X., M.M.A.); Polymat, University of the Basque Country, San Sebastian, Spain (A.A.); IMMA-CIOCC, Fundación Hospital de Madrid, Madrid, Spain (A.A.); Fundación Jimenez-Díaz, Madrid, Spain (J.G.-F.); Complejo Hospitalario de Navarra, Pamplona, Spain (T.T., I.Z.); Pitié-Salpètriere, Paris, France (S.P., J.Y.D.).
出版信息
Neuro Oncol. 2014 Apr;16(4):520-7. doi: 10.1093/neuonc/not218. Epub 2014 Jan 16.
BACKGROUND
Glioblastoma multiforme (GBM) is the most frequent malignant brain tumor in adults, and its prognosis remains dismal despite intensive research and therapeutic advances. Diagnostic biomarkers would be clinically meaningful to allow for early detection of the tumor and for those cases in which surgery is contraindicated or biopsy results are inconclusive. Recent findings show that GBM cells release microvesicles that contain a select subset of cellular proteins and RNA. The aim of this hypothesis-generating study was to assess the diagnostic potential of miRNAs found in microvesicles isolated from the serum of GBM patients.
METHODS
To control disease heterogeneity, we used patients with newly diagnosed GBM. In the discovery stage, PCR-based TaqMan Low Density Arrays followed by individual quantitative reverse transcriptase polymerase chain reaction were used to test the differences in the miRNA expression levels of serum microvesicles among 25 GBM patients and healthy controls paired by age and sex. The detected noncoding RNAs were then validated in another 50 GBM patients.
RESULTS
We found that the expression levels of 1 small noncoding RNA (RNU6-1) and 2 microRNAs (miR-320 and miR-574-3p) were significantly associated with a GBM diagnosis. In addition, RNU6-1 was consistently an independent predictor of a GBM diagnosis.
CONCLUSIONS
Altogether our results uncovered a small noncoding RNA signature in microvesicles isolated from GBM patient serum that could be used as a fast and reliable differential diagnostic biomarker.
背景
多形性胶质母细胞瘤（GBM）是成人中最常见的恶性脑肿瘤，尽管进行了深入的研究和治疗进展，但其预后仍然不佳。诊断生物标志物将具有重要的临床意义，可以早期发现肿瘤，并且对于手术禁忌或活检结果不确定的病例也有帮助。最近的研究结果表明，GBM 细胞释放含有细胞蛋白和 RNA 选择子集的微小囊泡。本假说生成研究旨在评估从 GBM 患者血清中分离的微小囊泡中发现的 miRNAs 的诊断潜力。
方法
为了控制疾病异质性，我们使用了新诊断为 GBM 的患者。在发现阶段，使用基于 PCR 的 TaqMan 低密度阵列，然后进行个体定量逆转录聚合酶链反应，以测试 25 名 GBM 患者和年龄和性别配对的健康对照者血清微小囊泡中 miRNA 表达水平的差异。然后在另外 50 名 GBM 患者中验证检测到的非编码 RNA。
结果
我们发现 1 种小非编码 RNA（RNU6-1）和 2 种 microRNAs（miR-320 和 miR-574-3p）的表达水平与 GBM 诊断显着相关。此外，RNU6-1 一直是 GBM 诊断的独立预测因子。
结论
总之，我们的研究结果揭示了 GBM 患者血清中分离的微小囊泡中的小非编码 RNA 特征，可作为一种快速可靠的差异诊断生物标志物。
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