| Autor: |
Giuseppina Sannino, Aruna Marchetto, Andreas Ranft, Susanne Jabar, Constanze Zacherl, Rebeca Alba-Rubio, Stefanie Stein, Fabienne S. Wehweck, Merve M. Kiran, Tilman L.B. Hölting, Julian Musa, Laura Romero-Pérez, Florencia Cidre-Aranaz, Maximilian M.L. Knott, Jing Li, Heribert Jürgens, Ana Sastre, Javier Alonso, Willian Da Silveira, Gary Hardiman, Julia S. Gerke, Martin F. Orth, Wolfgang Hartmann, Thomas Kirchner, Shunya Ohmura, Uta Dirksen, Thomas G.P. Grünewald |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
|
| Zdroj: |
EBioMedicine, Vol 47, Iss , Pp 156-162 (2019) |
| Druh dokumentu: |
article |
| ISSN: |
2352-3964 |
| DOI: |
10.1016/j.ebiom.2019.08.002 |
| Popis: |
Background: Up to 30–40% of Ewing sarcoma (EwS) patients with non-metastatic disease develop local or metastatic relapse within a time span of 2–10 years. This is in part caused by the absence of prognostic biomarkers that can identify high-risk patients and thus assign them to risk-adapted monitoring and treatment regimens. Since cancer stemness has been associated with tumour relapse and poor patient outcomes, we investigated in the current study the prognostic potential SOX2 (sex determining region Y box 2) – a major transcription factor involved in development and stemness – which was previously described to contribute to the undifferentiated phenotype of EwS. Methods: Two independent patient cohorts, one consisting of 189 retrospectively collected EwS tumours with corresponding mRNA expression data (test-cohort) and the other consisting of 141 prospectively collected formalin-fixed and paraffin-embedded resected tumours (validation and cohort), were employed to analyse SOX2 expression levels through DNA microarrays or immunohistochemistry, respectively, and to compare them with clinical parameters and patient outcomes. Two methods were employed to test the validity of the results at both the mRNA and protein levels. Findings: Both cohorts showed that only a subset of EwS patients (16–20%) expressed high SOX2 mRNA or protein levels, which significantly correlated with poor overall survival. Multivariate analyses of our validation-cohort revealed that high SOX2 expression represents a major risk-factor for poor survival (HR = 3·19; 95%CI 1·74–5·84; p |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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