Zuo Shan-Ru, Zuo Xiao-Cong, He Yang, Fang Wei-Jin, Wang Chun-Jiang, Zou Heng, Chen Pan, Huang Ling-Fei, Huang Li-Hua, Xiang Hong, Liu Shi-Kun
Department of Center Clinical Pharmacology and Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, China.
Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, China.
J Cancer. 2018 Jan 1;9(2):321-330. doi: 10.7150/jca.22218. eCollection 2018.
SET and MYND domain-containing protein2 (SMYD2), a histone lysine methyltransferases, is a candidate human oncogene in multiple tumors. However, the expression dynamics of SMYD2 in hepatocellular carcinoma (HCC) and its clinical/prognostic significance are unclear. The SMYD2 expression profile was examined by quantitative real-time polymerase chain reaction (qRT-PCR), and immunohistochemistry (IHC) in HCC tissues and matched adjacent non-tumorous tissues. SMYD2 was silenced in HCC cell lines to determine its role in tumor proliferation and cell cycle progression, and the possible mechanism. Spearman's rank correlation, Kaplan-Meier plots and Cox proportional hazards regression model were used to analyze the data. The SMYD2 expression in HCC tissues were significantly up-regulated at both mRNA and protein levels as compared with the matched adjacent non-tumorous tissues. By IHC, positive expression of SMYD2 was examined in 122/163 (74.85%) of HCC and in 10/59 (16.95%) of tumor-adjacent tissues. Positive expression of SMYD2 was correlated with tumor size, vascular invasion, differentiation and TNM stage ( < 0.05). In univariate survival analysis, a significant association between positive expression of SMYD2 and shortened patients' survival was found ( < 0.05). Importantly, SMYD2 expression together with vascular invasion ( < 0.05) provided significant independent prognostic parameters in multivariate analysis. Functionally, SMYD2 silenced markedly inhibited cell proliferation and cell cycle progression in SMMC-7721 cell. Our findings provide evidences that positive expression of SMYD2 in HCC may be important in the acquisition of an aggressive phenotype, and it is an independent biomarker for poor prognosis of patients with HCC.
含SET和MYND结构域蛋白2（SMYD2）是一种组蛋白赖氨酸甲基转移酶，是多种肿瘤中潜在的人类癌基因。然而，SMYD2在肝细胞癌（HCC）中的表达动态及其临床/预后意义尚不清楚。通过定量实时聚合酶链反应（qRT-PCR）和免疫组织化学（IHC）检测了HCC组织及配对的癌旁非肿瘤组织中SMYD2的表达情况。在HCC细胞系中沉默SMYD2以确定其在肿瘤增殖和细胞周期进程中的作用及其可能机制。采用Spearman等级相关分析、Kaplan-Meier生存曲线分析和Cox比例风险回归模型进行数据分析。与配对的癌旁非肿瘤组织相比，HCC组织中SMYD2在mRNA和蛋白水平均显著上调。通过IHC检测发现，163例HCC中有122例（74.85%）SMYD2呈阳性表达，59例癌旁组织中有10例（16.95%）呈阳性表达。SMYD2的阳性表达与肿瘤大小、血管侵犯、分化程度及TNM分期相关（P<0.05）。单因素生存分析发现，SMYD2阳性表达与患者生存期缩短显著相关（P<0.05）。重要的是，在多因素分析中，SMYD2表达与血管侵犯（P<0.05）共同构成了显著的独立预后参数。功能上，沉默SMYD2可显著抑制SMMC-7721细胞的增殖和细胞周期进程。我们的研究结果表明，HCC中SMYD2的阳性表达可能在侵袭性表型的获得中起重要作用，并且是HCC患者预后不良的独立生物标志物。
