Up regulation and nuclear translocation of Y-box binding protein 1 (YB-1) is linked to poor prognosis in ERG-negative prostate cancer

盒结合蛋白 1 (YB-1) 的上调和核易位与 ERG 阴性前列腺癌的预后不良有关

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作者:Asmus Heumann, Özge Kaya, Christoph Burdelski, Claudia Hube-Magg, Martina Kluth, Dagmar S Lang, Ronald Simon, Burkhard Beyer, Imke Thederan, Guido Sauter, Jakob R Izbicki, Andreas M Luebke, Andrea Hinsch, Frank Jacobsen, Corinna Wittmer, Franziska Büscheck, Doris Höflmayer, Sarah Minner, Maria Chris

Abstract

Y-box binding protein 1 (YB-1) is an RNA and DNA binding factor with potential prognostic cancer. To evaluate the clinical impact of YB-1, a tissue microarray with 11,152 prostate cancers was analysed by immunohistochemistry. Cytoplasmic and nuclear staining was separately analysed. Cytoplasmic YB-1 was absent or weak in normal epithelium but seen in 86,3% of carcinomas. Cytoplasmic staining was weak, moderate, and strong in 29.6%, 43.7% and 13.0% of tumours and was accompanied by nuclear YB-1 staining in 32.1% of cases. Particularly nuclear staining was strongly linked to poor patient prognosis (p < 0.0001). YB-1 protein was more abundant in ERG positive (95.1%) than in ERG negative cancers (80.4%; p < 0.0001), but any prognostic impact of YB-1 staining was limited to the ERG-negative subset. Similarly, significant associations with pT stage and Gleason grade (p < 0.0001 each) were driven by the ERG negative subset. The significant association of YB-1 protein detection with deletions of PTEN, 5q21 and 6q15 fits well in the protein's role as an inhibitor of DNA damage dependent cell cycle arrest, a role that is likely to induce genomic instability. In summary, the data show, that the prognostic impact of YB-1 expression is limited to ERG negative prostate cancers.

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