Abstract
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.
| Original language | English |
|---|---|
| Journal | Journal of Neuro-Oncology |
| Volume | 115 |
| Issue number | 3 |
| Pages (from-to) | 453-61 |
| Number of pages | 9 |
| ISSN | 0167-594X |
| DOIs | |
| Publication status | Published - Dec 2013 |
| Externally published | Yes |
Keywords
- Adult
- Biomarkers, Tumor/metabolism
- Brain Neoplasms/epidemiology
- Denmark/epidemiology
- Female
- Follow-Up Studies
- Glioma/epidemiology
- Humans
- Male
- Middle Aged
- Neoplasm Grading
- Neoplastic Stem Cells/metabolism
- Nerve Tissue Proteins/metabolism
- Prognosis
- RNA-Binding Proteins/metabolism
- Survival Rate
- Tissue Array Analysis
- World Health Organization
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