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[摘要]
目的:探讨小脑锌指结构1 (zinc finger protein of the cerebellum 1,ZIC1)基因在人子宫内膜癌组织中的表达情况及其与临床参数之间的关系和预后预测价值。 方法: 收集江苏大学附属昆山医院及上海市第六人民医院自2008年1月至2011年12月收治的子宫内膜癌患者43例,取肿瘤组织及相应的距原发灶边缘2 cm以上的癌旁黏膜组织标本。应用免疫组织化学法、Western blot-ting及RT-PCR法检测43例子宫内膜癌原发灶组织及癌旁黏膜组织中ZIC1的表达,分析其与临床病理参数之间的关系,并通过5年生存情况分析评价其预后价值。 结果:子宫内膜癌组织中ZIC1的mRNA水平和蛋白水平均明显高于癌旁组织。ZIC1蛋白在子宫内膜癌组织中呈现高表达,其阳性表达率为72.1%(31/43),在癌旁组织中阳性表达率为39.5%(17/43)。ZIC1 mRNA的表达与淋巴结转移及FIGO分期有关(P<0.01或P<0.05)。ZIC1低表达患者的5年生存率明显高于高表达患者(66.7% vs 38.7%,P< 0.05)。单因素分析发现ZIC1 (高表达 vs低表达)风险比(HR)为2.66,95%CI: 1.07-5.89,P=0.047;经多因素分析调整后,HR=2.25,95%CI: 1.36-3.71,P=0.002,说明高水平的ZIC1与子宫内膜癌术后预后不良密切相关。 结论: ZIC1表达水平的升高在子宫内膜癌的发生发展中起着重要作用,可能成为子宫内膜癌治疗和预后测评的一个新的指标。
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[Abstract]
Objective: The aim of this study was to determine the expression of zinc finger protein of the cerebellum 1 (ZIC1) in endometrial cancer tissues, and to investigate its correlation to clinical parameters as well as it prognostic value. Methods: We selected 43 endometrial cancer patients from Kunshan First People’s Hospital Affiliated to Ji-angsu University and Shanghai No.6 People’s Hospital during January 2008 to November 2011, and collected tumor tissues and corresponding para-carcinoma tissues (2 cm or more away from the primary lesion). Immunohistochemis-try, Western blotting and RT-PCR were used to determine the expressions of ZIC1 in 43 endometrial cancer samples as well as the normal adjacent tissues; the association between ZICI expression and clinicopathological parameters were analyzed, and its prognostic value was investigated through 5-year survival analysis. Results:Asignificantly in-creased expression of ZIC1 was observed in endometrial cancer tissues compared to that in para-carcinoma tissues,for both mRNAand protein levels through RT-PCR and Western blotting (P<0.05). ZIC1 was highly expressed in en-dometrial cancer samples with a positive rate of 72.1% (31/43), while the positive rate in para-carcinoma tissues were 39.5% (17/43). Moreover, ZIC1 mRNAwas significantly correlated with lymph node metastasis and FIGO stag-ing (P<0.05); the 5-year survival of ZIC1 - patients was significantly higher than that of ZIC1+patients (66.7% vs 38.7%,P<0.05). Univariant analysis revealed that the hazard ratio (HR) of ZIC1 (high expression vs low expression)was 2.66, 95%CI: 1.07-5.89,P=0.047; and after the adjustment of multivariate analysis, the result showed HR=2.25,95%CI: 1.36-3.71,P=0.002, indicating high level ZIC1 was closely related to the poor prognosis after endometrial surgery. Conclusions: ZIC1 plays an important role in the occurrence and development of endometrial adenocarcino-ma and may be served as a promising target for the therapy and prognosis of endometrial adenocarcinoma.
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[基金项目]
江苏大学医学临床科技发展基金资助项目(No. JLY20120050)