Hypomethylation of BORIS is a promising prognostic biomarker in hepatocellular carcinoma
Hypomethylation of BORIS is a promising prognostic biomarker in hepatocellular carcinoma
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DOI：
10.1016/j.gene.2017.07.077
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发表时间：
2017-09-20
期刊：
影响因子：
3.5
通讯作者：
Qin, Yang
中科院分区：
文献类型：
--
作者：
He, Jingyang;Huang, Yuan;Qin, Yang
印记位点调节器 (BORIS) 的兄弟是一种 11 锌指 (ZF) 蛋白，是 CCCTC 结合因子 (CTCF) 的旁系同源物，参与染色质功能的一些关键事件以及精子发生过程中的复杂转录调节。作为一种新的肿瘤癌基因，BORIS 在人肝细胞癌中观察到异常表达，但其潜在机制仍有待探索。在这项研究中，通过甲基化特异性聚合酶链反应（MSP）在人肝癌细胞系和43对组织标本中检测了BORIS的甲基化状态。 HCC 中 BORIS 的去甲基化程度显着高于配对的邻近非肿瘤组织（P = 0.019），并且与肿瘤大小（P = 0.025）和临床 TNM 分期（P = 0.035）相关。低甲基化 BORIS 患者的无病生存期比未去甲基化 BORIS 的患者短（P = 0.006）。此外，Cox回归分析表明，BORIS去甲基化状态是HCC患者总生存率降低的独立风险（P = 0.035）。这些发现为阐明去甲基化是否可能导致启动子激活以上调 BORIS 表达提供了线索。总之，异常的 BORIS 低甲基化是 HCC 预后的一个有前途的生物标志物。
The brother of the regulator of the imprinted site (BORIS), an 11 zinc finger (ZF) protein, is a paralogue of CCCTC-binding factor (CTCF), involves in a few crucial events of chromatin functions, complex transcription regulation during spermatogenesis. As a novel tumor oncogene, abnormal expression of BORIS is observed in human hepatocellular carcinoma, however, the underlying mechanisms remain largely unexplored. In this study, the methylation status of BORIS was tested by methylation specific polymerase chain reaction (MSP) in human HCC cell lines and 43 pairs of tissue specimens. Frequently demethylation of BORIS in HCC was significantly higher than that in the paired adjacent non-tumor tissues (P = 0.019), and it was correlated with tumor size (P = 0.025) and clinical TNM stage (P = 0.035). Patients with hypomethylated BORIS had a shorter disease free survival than those without demethylated BORIS (P = 0.006). Further, analyses using Cox regression have indicated that the BORIS demethylation status was an independent risk to the reduced overall survival rate of HCC patients (P = 0.035). These findings provide clues to clarify whether the demethylation may lead to activation of the promoter for upregulation expression of BORIS. In conclusions, aberrant BORIS hypomethylation is a promising biomarker for the prognosis of HCC.