Expression of Ret finger protein correlates with outcomes in endometrial cancer

Expression of Ret finger protein correlates with outcomes in endometrial cancer
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DOI:
10.1111/j.1349-7006.2009.01278.x
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发表时间:
2009-10-01
期刊:
影响因子:
5.7
通讯作者:
Takahashi, Masahide
Takahashi, Masahide
中科院分区:
医学2区
文献类型:
--
作者:
Tsukamoto, Hirohisa;Kato, Takuya;Takahashi, Masahide

文献摘要

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Ret指蛋白(RFP)是一种具有转录抑制活性的核蛋白,在多种人类和啮齿动物肿瘤细胞系中高度表达。我们检测了RFP在人子宫内膜癌中的表达,并评估其临床意义。用RFP抗体对来自子宫内膜癌组织的福尔马林固定、石蜡包埋切片进行免疫染色,并评价染色强度。研究的临床病理因素包括年龄、国际妇产科联合会分期、肿瘤分级、肌层浸润和盆腔淋巴结转移。采用Kaplan-Meier法评价总生存期(OS)和无进展生存期(PFS),采用考克斯比例风险分析进行多变量分析。119例癌组织中RFP阳性57例(47.9%)。RFP的表达与任何临床病理参数无关。然而,与阴性表达相比,RFP阳性表达显著预测了较差的OS和PFS(OS,P = 0.0011; PFS,P < 0.0001)。在多变量分析中,RFP阳性表达是本研究中生存的独立预后因素。RFP敲除显著损害了体外癌细胞的迁移和侵袭,伴随着整合素β 1和α 2的减少。RFP阳性表达是子宫内膜癌患者不良临床结局的预测标志物。(Cancer Sci 2009; 100:1895-1901)。
Ret finger protein (RFP) is a nuclear protein with transcriptional repressive activity that is highly expressed in a variety of human and rodent tumor cell lines. We examined the expression of RFP in human endometrial cancer and assessed its clinical significance. Formalin-fixed, paraffin-embedded sections from endometrial cancer tissues were immunostained with the RFP antibody, and the staining intensity was evaluated. The clinicopathological factors examined were age, International Federation of Gynecology and Obstetrics stage, tumor grade, myometrial invasion, and pelvic lymph node metastasis. Overall survival (OS) and progression-free survival (PFS) were evaluated using the Kaplan-Meier method, and multivariate analysis was performed using the Cox proportional hazard analysis. Of the 119 cancer tissues, 57 (47.9%) cases were positive for RFP immunoreactivity. RFP expression was not associated with any of the clinicopathological parameters examined. However, positive RFP expression significantly predicted poorer OS and PFS compared with negative expression (OS, P = 0.0011; PFS, P < 0.0001). In the multivariate analyses, positive RFP expression was an independent prognostic factor for survival in this study. RFP knockdown significantly impaired cancer cell migration and invasion in vitro with concomitant decreases of integrins beta 1 and alpha 2. Positive RFP expression is a predictive marker for an unfavorable clinical outcome in patients with endometrial cancer. (Cancer Sci 2009; 100: 1895-1901).