J Cancer 2018; 9(2):321-330. doi:10.7150/jca.22218 This issue

Research Paper

Positive Expression of SMYD2 is Associated with Poor Prognosis in Patients with Primary Hepatocellular Carcinoma

Shan-Ru Zuo1, Xiao-Cong Zuo1, Yang He1, Wei-Jin Fang1, Chun-Jiang Wang1, Heng Zou2, Pan Chen3, Ling-Fei Huang4, Li-Hua Huang5, Hong Xiang5, Shi-Kun Liu1✉

1. Department of Center Clinical Pharmacology and Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, China;
2. Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, China;
3. Department of Hepatobiliary Surgery, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China;
4. Department of Obstetrics and Gynecology, Taizhou Hospital of Zhe Jiang Province, Taizhou, China;
5. Center for Experimental Medicine Research, The Third Xiangya Hospital, Central South University, Changsha, China.

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Zuo SR, Zuo XC, He Y, Fang WJ, Wang CJ, Zou H, Chen P, Huang LF, Huang LH, Xiang H, Liu SK. Positive Expression of SMYD2 is Associated with Poor Prognosis in Patients with Primary Hepatocellular Carcinoma. J Cancer 2018; 9(2):321-330. doi:10.7150/jca.22218. Available from https://www.jcancer.org/v09p0321.htm

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Purpose: 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.

Methods: 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.

Results: 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 (P < 0.05). In univariate survival analysis, a significant association between positive expression of SMYD2 and shortened patients' survival was found (P < 0.05). Importantly, SMYD2 expression together with vascular invasion (P < 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.

Conclusions: 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.

Keywords: SMYD2, hepatocellular carcinoma, immunohistochemistry, prognosis.