Protein phosphatase 1 nuclear-targeting subunit (PNUTS) is ubiquitously expressed and associates with PTEN and protein phosphatase 1 (PP1) to control its activity. The role of PNUTS overexpression has hardly been studied in cancer. In this study, we used immunohistochemistry to quantitate PNUTS expression on a tissue microarray containing 17,747 clinical prostate cancer specimens. As compared to normal prostate epithelium, PNUTS expression was often higher in cancer. Among 12,235 interpretable tumors, PNUTS staining was negative in 21%, weak in 34%, moderate in 35%, and strong in 10% of cases. High PNUTS expression was associated with higher tumor stage, classical and quantitative Gleason grade, nodal stage, surgical margin, Ki67 labeling index, and early biochemical recurrence ( each). PNUTS expression proved to be a moderate prognostic parameter with a maximal univariable Cox proportional hazard for PSA recurrence-free survival of 2.21 compared with 5.91 for Gleason grading. It was independent from established prognostic parameters in multivariable analysis. Comparison with molecular data available from earlier studies using the same TMA identified associations between high PNUTS expression and elevated androgen receptor expression (), presence of TMPRSS2:ERG fusion (), and 8 of 11 chromosomal deletions (3p13, 5q21, 8p21, 10q23, 12p13, 13q14, 16q24, and 17p13; each). Particularly strong associations with PTEN and 12p13 deletions ( each) may indicate a functional relationship, which has already been established for PNUTS and PTEN. PNUTS had no additional role on outcome in PTEN-deleted cancers. In conclusion, the results of our study identify high PNUTS protein levels as a predictor of poor prognosis possibly linked to increased levels of genomic instability. PNUTS measurement, either alone or in combination, might be of clinical utility in prostate cancers.

中文翻译：

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磷酸酶1核靶向亚单位（PNUTS）的上调是前列腺癌预后不良的独立预测因子。

蛋白磷酸酶1核靶向亚基（PNUTS）随处可见，并与PTEN和蛋白磷酸酶1（PP1）结合以控制其活性。几乎没有研究过PNUTS过表达的作用。在这项研究中，我们使用免疫组织化学定量了包含17747个临床前列腺癌标本的组织微阵列上PNUTS的表达。与正常前列腺上皮相比，PNUTS表达在癌症中通常更高。在12235种可解释的肿瘤中，PNUTS染色阴性的占21％，弱的占34％，中度的占35％，强的占10％。PNUTS高表达与较高的肿瘤分期，经典的和定量的格里森分级，淋巴结分期，手术切缘，Ki67标记指数和早期生化复发相关（每）。PNUTS表达被证明是一个适度的预后参数，PSA无复发生存期的最大单变量Cox比例风险为2.21，格里森分级为5.91。它独立于多变量分析中已建立的预后参数。与使用相同TMA的较早研究提供的分子数据进行比较，确定了PNUTS高表达与雄激素受体表达升高之间的关联（），存在TMPRSS2：ER G融合（）和11个染色体缺失中的8个（3p13、5q21、8p21、10q23、12p13、13q14、16q24和17p13；每）。与PTEN和12p13缺失特别紧密的关联（每个）可能表示已经为PNUTS和PTEN建立的功能关系。在删除PTEN的癌症中，PNUTS对结局没有附加作用。总之，我们的研究结果确定高PNUTS蛋白水平可作为不良预后的预测因素，可能与基因组不稳定水平增加有关。单独或组合使用PNUTS测量可能在前列腺癌中具有临床实用性。