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

Abstract

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.

The Promise for Histone Methyltransferase Inhibitors for Epigenetic Therapy in Clinical Oncology: A Narrative Review

“…A recent report found abundant expression of SMYD2 to be an independent biomarker for poor prognosis of patients with hepatocellular carcinoma, which might imply that SMYD2 overexpression is associated with a more aggressive phenotype [ 169 ]. Potent and selective SMYD2 inhibitors have been developed to interrogate this potentially important anticancer approach [ 170 – 172 ].…”

MiR-494-3p promotes PI3K/AKT pathway hyperactivation and human hepatocellular carcinoma progression by targeting PTEN

“…Many oncogenes, growth factors, and tumor suppressor genes have been identified in processes of hepatocarcinogenesis 22 – 25 , however, the molecular carcinogenic mechanisms and the pathogenic biology of HCC remains unclear 22 , 26 – 28 . A growing amount of experimental evidence has been supporting a significant role for miRNAs in tumorigenesis of HCC 27 , 29 , 30 .…”

Pathogenic and Therapeutic Role of H3K4 Family of Methylases and Demethylases in Cancers

“…SMYD3 act as a prognostic parameter in HCC and PCa [55,56]. Similarly, SMYD2 was found to have independent prognostic value for patients with primary HCC and papillary thyroid carcinoma [57,58]. The deregulation of various H3K4 methyltransferases in cancers is summarized in Table 2.…”