Department of Oncology, Odense University Hospital, Sdr. Boulevard 29, 5000, Odense, Denmark,
J Neurooncol. 2013 Dec;115(3):453-61. doi: 10.1007/s11060-013-1246-8. Epub 2013 Sep 21.
The aim of this study was to investigate the prognostic value of the RNA-binding protein Musashi-1 in adult patients with primary gliomas. Musashi-1 has been suggested to be a cancer stem cell-related marker in gliomas, and high levels of Musashi-1 have been associated with high tumor grades and hence poor prognosis. Samples of 241 gliomas diagnosed between 2005 and 2009 were stained with an anti-Musashi-1 antibody using a fluorescent staining protocol followed by automated image acquisition and processing. Musashi-1 area fraction and intensity in cytoplasm and in nuclei were quantified by systematic random sampling in 2 % of the vital tumor area. In WHO grade III tumors high levels of Musashi-1 were associated with poor survival in multivariate analysis (HR 3.39, p = 0.02). We identified a sub-population of glioblastoma (GBM) patients with high levels of Musashi-1 and a superior prognosis (HR 0.65, p = 0.038). In addition patients with high levels of Musashi-1 benefitted most from post-surgical treatment, indicating that Musashi-1 may be a predictive marker in GBMs. In conclusion, our results suggest that high levels of Musashi-1 are associated with poor survival in patients with WHO grade III tumors and that Musashi-1 may be a predictive marker in GBMs, although further validation is needed. We find the combination of immunofluorescence and automated quantitation to be a feasible, robust, and reproducible approach for quantitative biomarker studies.
本研究旨在探讨 RNA 结合蛋白 Musashi-1 在成人原发性脑胶质瘤患者中的预后价值。Musashi-1 已被认为是胶质瘤中与癌症干细胞相关的标志物,高水平的 Musashi-1 与高肿瘤分级相关,因此预后不良。对 2005 年至 2009 年间诊断的 241 例脑胶质瘤样本进行了荧光染色,并使用抗 Musashi-1 抗体进行染色,随后进行自动图像采集和处理。通过系统随机抽样,在 2%的肿瘤活跃区域内对细胞质和细胞核中的 Musashi-1 面积分数和强度进行定量。在 WHO 分级 III 级肿瘤中,高水平的 Musashi-1 在多变量分析中与不良生存相关(HR 3.39,p = 0.02)。我们鉴定出一组高水平 Musashi-1 的胶质母细胞瘤(GBM)患者具有较好的预后(HR 0.65,p = 0.038)。此外,高水平 Musashi-1 的患者从手术后治疗中获益最大,表明 Musashi-1 可能是 GBM 的预测标志物。总之,我们的研究结果表明,高水平的 Musashi-1 与 WHO 分级 III 级肿瘤患者的不良生存相关,而 Musashi-1 可能是 GBM 的预测标志物,尽管需要进一步验证。我们发现免疫荧光和自动定量相结合是一种可行、稳健和可重复的定量生物标志物研究方法。