Orphan Nuclear Receptor TR3/Nur77 is a Specific Therapeutic Target for Hepatic Cancers.
Orphan Nuclear Receptor TR3/Nur77 is a Specific Therapeutic Target for Hepatic Cancers.
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DOI：
10.4172/2324-9110.1000184
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发表时间：
2017-05
期刊：
影响因子：
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通讯作者：
Yingling Zeng;X. Ye;D. Liao;Shizhang Huang;Huinan Mao;Dezheng Zhao;H. Zeng
中科院分区：
文献类型：
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作者：
Yingling Zeng;X. Ye;D. Liao;Shizhang Huang;Huinan Mao;Dezheng Zhao;H. Zeng
目的：虽然癌症治疗取得了巨大的成功，但目前的癌症治疗方法，包括抗肿瘤和抗血管生成，仍然面临着疗效不足、耐药和内在难治性以及毒副作用的问题。有必要确定可以阻断的其他靶标，以关闭大多数（如果不是全部的话）途径的下游影响。我们之前的研究表明孤儿核受体TR3（人）/ Nur77（小鼠）就是这样一个靶点。然而，TR3表达与临床肿瘤进展的相关性尚未得到研究。方法采用免疫组化染色法对病历完整的人原发性肝癌标本中TR3的表达进行分析。采用统计学方法评价TR3在肿瘤组织、瘤旁组织和正常组织中的表达，探讨TR3表达与临床病理特征的相关性。结果TR3在人肝癌组织中高表达，而在正常肝组织中不表达。TR3在癌组织、癌旁组织和正常肝组织中的阳性表达率分别为67.67%（14/21）、19.05%（4/21）、0%(0/10)，差异均有统计学意义（χ2=17.07, p<0.005）。TR3在癌组织和正常组织中的表达均显著高于癌旁组织（χ2=9.722, p<0.005）和正常组织（p<0.0005）。人肝癌组织中TR3表达水平与肿瘤中低分化程度、门静脉血栓形成、转移、复发相关，与年龄、性别、肿瘤数量、甲胎蛋白（AFP）量无关。结论TR3是治疗肝癌的特异性靶点。
OBJECTIVE Although great success has been achieved in cancer treatment, current cancer therapies, including anti-tumorigenesis and anti-angiogenesis, still face the problems of insufficient efficacy, resistance and intrinsic refractoriness, in addition to their toxic side effects. There is a demand to identify additional targets that can be blocked to turn off the downstream effects of most, if not all, pathways. Our previous studies suggest that orphan nuclear receptor TR3 (human) / Nur77 (mouse) is such a target. However, the correlation of TR3 expression and clinical tumor progression has not been studied. METHODS The expression of TR3 was analysed in human primary hepatic cancer specimens from patients that have complete medical records with Immunohistochemical staining. The statistical analysis was used to assess the significance of TR3 expression in tumor tissues, paratumor tissues and normal tissues, and to investigate the correlation of TR3 expression and clincopathologic characteristics. RESULTS TR3 is highly expressed in human hepatic cancer tissues, but not in normal liver tissues. The positive expression yields of TR3 are 67.67% (14/21), 19.05% (4/21) and 0% (0/10) in cancer tissues, para cancer tissues, and normal liver tissue, respectively, which are statistic significant (χ2=17.07, p<0.005). The expression of TR3 is significantly higher in cancer tissues than in para cancer tissues χ2=9.722, p<0.005) and in normal tissues (p<0.0005). The levels of TR3 expression in human hepatic cancer tissues correlates well with tumors that are at low/middle degree of tumor differentiation and have portal vein thrombosis, metastasis and recurrence, but not with age, gender, tumor number and Alpha-fetal protein (AFP) volume. CONCLUSION The results indicate that TR3 is a specific therapeutic target for hepatic cancers.