Fei Xiao, Ma Yun, Liu Xiaowei, Meng Zhixin
Department of Infectious Disease, Yidu Central Hospital.
Department of Intensive Care Unit, Yidu Central Hospital.
Tohoku J Exp Med. 2017 Nov;243(3):219-226. doi: 10.1620/tjem.243.219.
SET and MYND domain-containing protein 3 (SMYD3) is a kind of histone lysine methyltransferase, responsible for transcriptional activation as a member of an RNA polymerase complex. The ectopic expression of SMYD3 is proved to promote the progress of many kinds of cancers. In hepatocellular carcinoma (HCC), SMYD3 was demonstrated to promote the proliferation and metastasis of HCC cell lines, but the clinical significance of SMYD3 has not been elucidated. In the present study, we detected the expression of SMYD3 in 100 HCC tissues with immunohistochemistry and divided these tissue specimens into high-expression group and low-expression group according to the immunohistochemical score of SMYD3. Importantly, the intensity of SMYD3 immunoreactivity was significantly stronger in HCC tissues than that in adjacent normal tissues. Moreover, high expression levels of SMYD3 were significantly associated with larger tumor size (P = 0.043), suggesting that SMYD3 could promote the proliferation of HCC. Moreover, patients with positive hepatitis B virus infection had higher expression levels of SMYD3 (P = 0.013). With univariate and multivariate analysis, we explored the prognostic significance of SMYD3 in HCC. As a result, high expression levels of SMYD3 were significantly correlated to the poorer clinical outcome of HCC patients (P = 0.009) and were identified as an independent risk factor of HCC for predicting the unfavorable prognosis. In conclusion, overexpression of SMYD3 is an independent prognostic risk of unfavorable prognosis of HCC. We propose that the anti-SMYD3 therapy may be a potential approach to treat HCC.
含SET和MYND结构域蛋白3(SMYD3)是一种组蛋白赖氨酸甲基转移酶,作为RNA聚合酶复合物的成员负责转录激活。已证实SMYD3的异位表达会促进多种癌症的进展。在肝细胞癌(HCC)中,已证明SMYD3可促进HCC细胞系的增殖和转移,但SMYD3的临床意义尚未阐明。在本研究中,我们采用免疫组织化学方法检测了100例HCC组织中SMYD3的表达,并根据SMYD3的免疫组织化学评分将这些组织标本分为高表达组和低表达组。重要的是,HCC组织中SMYD3免疫反应性的强度明显强于相邻正常组织。此外,SMYD3高表达水平与更大的肿瘤大小显著相关(P = 0.043),这表明SMYD3可促进HCC的增殖。此外,乙型肝炎病毒感染阳性的患者SMYD3表达水平更高(P = 0.013)。通过单因素和多因素分析,我们探讨了SMYD3在HCC中的预后意义。结果,SMYD3高表达水平与HCC患者较差的临床结局显著相关(P = 0.009),并被确定为预测不良预后的HCC独立危险因素。总之,SMYD3的过表达是HCC不良预后的独立预后风险。我们认为抗SMYD3治疗可能是治疗HCC的一种潜在方法。