Up regulation and nuclear translocation of Y-box binding protein 1 (YB-1) is linked to poor prognosis in ERG-negative prostate cancer.
Up regulation and nuclear translocation of Y-box binding protein 1 (YB-1) is linked to poor prognosis in ERG-negative prostate cancer.
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DOI：
10.1038/s41598-017-02279-x
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发表时间：
2017-05-17
影响因子：
4.6
通讯作者：
Wilczak W
中科院分区：
文献类型：
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作者：
Heumann A;Kaya Ö;Burdelski C;Hube-Magg C;Kluth M;Lang DS;Simon R;Beyer B;Thederan I;Sauter G;Izbicki JR;Luebke AM;Hinsch A;Jacobsen F;Wittmer C;Büscheck F;Höflmayer D;Minner S;Tsourlakis MC;Schlomm T;Wilczak W
Y-box结合蛋白1 （YB-1）是一种与潜在预后癌相关的RNA和DNA结合因子。为了评估YB-1的临床影响，我们用免疫组织化学分析了11152例前列腺癌的组织芯片。细胞质染色和细胞核染色分别进行分析。胞质YB-1在正常上皮中缺失或弱，但在86.3%的癌中可见。29.6%、43.7%和13.0%的肿瘤细胞质染色为弱、中、强，32.1%的肿瘤伴核YB-1染色。特别是核染色与患者预后不良密切相关（p < 0.0001）。YB-1蛋白在ERG阳性肿瘤中含量（95.1%）高于ERG阴性肿瘤（80.4%,p < 0.0001），但YB-1染色对预后的影响仅限于ERG阴性肿瘤。同样，与pT分期和Gleason分级的显著关联（p < 0.0001）是由ERG阴性子集驱动的。YB-1蛋白检测与PTEN、5q21和6q15缺失的显著关联，很好地符合该蛋白作为DNA损伤依赖性细胞周期阻滞抑制剂的作用，这一作用可能会诱导基因组不稳定。总之，数据显示，YB-1表达对预后的影响仅限于ERG阴性前列腺癌。
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.