Cytoplasmic Mislocalization of the Orphan Nuclear Receptor Nurr1 Is a Prognostic Factor in Bladder Cancer
Cytoplasmic Mislocalization of the Orphan Nuclear Receptor Nurr1 Is a Prognostic Factor in Bladder Cancer
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DOI：
10.1002/cncr.24737
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发表时间：
2010-01-15
期刊：
影响因子：
6.2
通讯作者：
Kamat, Ashish M.
中科院分区：
文献类型：
--
作者：
Inamoto, Teruo;Czerniak, Bogdan A.;Kamat, Ashish M.
背景：Nurr1 属于一类新型孤儿核受体（NR4A 家族）。作者之前已经证明 Nurr1 在致癌过程中很重要。在当前的研究中，他们检查了膀胱肿瘤中 Nurr1 表达模式的临床病理相关性。方法：使用免疫组织化学染色测定膀胱癌组织阵列（145 个肿瘤）中的 Nurr1 表达。根据细胞质和细胞核中的 Nurr1 蛋白水平对肿瘤进行分类。通过多变量模型中的 Kaplan-Meier 分析和 Cox 比例风险分析研究疾病特异性生存率和无复发生存率，并与肿瘤分期、生长模式和临床结果（复发和生存）等变量相关。在体外，使用小干扰 RNA 沉默检查了 Nurr1 在膀胱癌细胞增殖和迁移中的作用。结果：肿瘤细胞中的 Nurr1 表达与肿瘤分期的增加和侵袭性生长模式相关。与细胞质 Nurr1 表达水平较低的患者相比，细胞质 Nurr1 表达水平较高的肿瘤患者的疾病特异性生存期显着缩短。此外，细胞质 Nurr1 表达水平被发现是疾病特异性生存的独立预测因子（比值比，4.894；P < .001）。在体外，内源性 Nurr1 的沉默减弱了膀胱癌细胞的迁移。结论：细胞质中 Nurr1 的表达与不良结局相关，是膀胱癌患者肿瘤进展和生存的独立预后标志物。这可能代表膀胱癌治疗的新靶点。癌症 2010；116：340-6。 (C) 2070 美国癌症协会。
BACKGROUND: Nurr1 belongs to a novel class of orphan nuclear receptors (the NR4A family). The authors have previously shown that Nurr1 is important in carcinogenesis. In the current study, they examined the clinicopathologic relevance of expression patterns of Nurr1 in bladder tumors. METHODS: Nurr1 expression was determined using immunohistochemical staining in a bladder cancer tissue array (145 tumors). Tumors were classified according to Nurr1 protein levels in both cytoplasm and nucleus. Disease-specific survival and recurrence-free survival were investigated by Kaplan-Meier analysis and Cox proportional hazards analysis in multivariate models and correlated with variables such as tumor stage, growth pattern, and clinical outcome (recurrence and survival). In vitro, Nurr1 was examined for its role in bladder cancer cell proliferation and migration using small interfering RNA silencing. RESULTS: Nurr1 expression in tumor cells correlated with increasing tumor stage and invasive growth pattern. Disease-specific survival was significantly shorter in patients whose tumors demonstrated a high level of cytoplasmic Nurr1 compared with those with lower levels of cytoplasmic Nurr1 expression. Furthermore, cytoplasmic Nurr1 expression level was found to be an independent predictor of disease-specific survival (odds ratio, 4.894; P < .001). In vitro, silencing of endogenous Nurr1 attenuated the migration of bladder cancer cells. CONCLUSIONS: The expression of Nurr1 in the cytoplasm correlates with adverse outcome and is an independent prognostic marker for tumor progression and survival in patients with bladder cancer. This might represent a novel target in bladder cancer therapy. Cancer 2010;116:340-6. (C) 2070 American Cancer Society.