Zeng Yingling, Ye Xiaoguang, Liao Degui, Huang Shizhang, Mao Huinan, Zhao Dezheng, Zeng Huiyan
Departments of Preventative Medicine, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, P. R. China.
Departments of Infectious Diseases, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, P. R. China.
J Clin Exp Oncol. 2017 Jun;6(3). doi: 10.4172/2324-9110.1000184. Epub 2017 May 9.
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.
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.
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.
The results indicate that TR3 is a specific therapeutic target for hepatic cancers.
尽管癌症治疗已取得巨大成功，但当前的癌症治疗方法，包括抗肿瘤发生和抗血管生成，除了有毒副作用外，仍面临疗效不足、耐药性和内在难治性等问题。需要确定可以阻断的其他靶点，以消除大多数（如果不是全部）信号通路的下游效应。我们之前的研究表明，孤儿核受体TR3（人类）/Nur77（小鼠）就是这样一个靶点。然而，尚未研究TR3表达与临床肿瘤进展的相关性。
采用免疫组织化学染色法分析有完整病历的人类原发性肝癌患者标本中TR3的表达。使用统计学分析评估TR3在肿瘤组织、癌旁组织和正常组织中表达的意义，并研究TR3表达与临床病理特征的相关性。
TR3在人类肝癌组织中高表达，但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）和0%（0/10），差异具有统计学意义（χ2=17.07，p<0.005）。TR3在癌组织中的表达明显高于癌旁组织（χ2=9.722，p<0.005）和正常组织（p<0.0005）。人类肝癌组织中TR3的表达水平与低/中度肿瘤分化、有门静脉血栓形成、转移和复发的肿瘤密切相关，但与年龄、性别、肿瘤数量和甲胎蛋白（AFP）水平无关。
结果表明TR3是肝癌的一个特异性治疗靶点。
